Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.ISUPPL.1.70
R. Hamilton, J. Pfau, G. Marshall, A. Holian
Some inhaled particles are known to lead to inflammation and lung pathology, whereas others do not appear to have long-term effects. Potential mechanisms to account for these differences are only beginning to be understood. In this article we examine whether silica and PM1648 (a model urban particulate) caused selective deletion of the suppressor human alveolar macrophage (HAM) phenotype (RFD1+/7+), and whether this affected cytokine production in an antigen-presenting cell (APC) assay with autologous T lymphocytes. HAM were exposed to the bioactive particulates, silica and PM1648, for 24 hours, then isolated free of extracellular particulates and nonviable cells; HAM were then cultured with autologous lymphocytes in an 11-day APC assay. Silica exposure up-regulated a TH1 lymphocyte-derived cytokine, interferon gamma (IFN-gamma), and a TH2 lymphocyte-derived cytokine, interleukin-4 (IL-4). PM1648 exposure primarily upregulated IL-4. Neither particle exposure had a significant effect on interleukin-10 (IL-10) production. Control particulate exposures with titanium dioxide (TiO2) and wollastonite (Woll) caused no altered APC activity. Silica and PM1648 demonstrated selective toxicity to suppressor macrophages (RFD1+/7+). We propose that, because of the suppressor macrophage phenotype disabling, the activator macrophage (RFD1+/7-) operates free of the suppressor macrophage's influence, enhancing APC activity with increased lymphocyte-derived proinflammatory cytokine production.
{"title":"Silica and PM1648 modify human alveolar macrophage antigen-presenting cell activity in vitro.","authors":"R. Hamilton, J. Pfau, G. Marshall, A. Holian","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.ISUPPL.1.70","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.ISUPPL.1.70","url":null,"abstract":"Some inhaled particles are known to lead to inflammation and lung pathology, whereas others do not appear to have long-term effects. Potential mechanisms to account for these differences are only beginning to be understood. In this article we examine whether silica and PM1648 (a model urban particulate) caused selective deletion of the suppressor human alveolar macrophage (HAM) phenotype (RFD1+/7+), and whether this affected cytokine production in an antigen-presenting cell (APC) assay with autologous T lymphocytes. HAM were exposed to the bioactive particulates, silica and PM1648, for 24 hours, then isolated free of extracellular particulates and nonviable cells; HAM were then cultured with autologous lymphocytes in an 11-day APC assay. Silica exposure up-regulated a TH1 lymphocyte-derived cytokine, interferon gamma (IFN-gamma), and a TH2 lymphocyte-derived cytokine, interleukin-4 (IL-4). PM1648 exposure primarily upregulated IL-4. Neither particle exposure had a significant effect on interleukin-10 (IL-10) production. Control particulate exposures with titanium dioxide (TiO2) and wollastonite (Woll) caused no altered APC activity. Silica and PM1648 demonstrated selective toxicity to suppressor macrophages (RFD1+/7+). We propose that, because of the suppressor macrophage phenotype disabling, the activator macrophage (RFD1+/7-) operates free of the suppressor macrophage's influence, enhancing APC activity with increased lymphocyte-derived proinflammatory cytokine production.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"124 1","pages":"75-84"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88014009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.20
S. Kaur, I. S. Grover, S. Kumar
Terminalia arjuna is an important medicinal plants widely used in the preparation of Ayurvedic formulations used against several ailments. The present investigation was aimed at the fractionation of crude extracts from the bark of T. arjuna in order to isolate and purify the antimutagenic factors present. The antimutagenicity assay was performed to check the modulatory effect of these fractions against NPD, sodium azide, and 2AF, using the Ames Salmonella his+ reversion assay. Most of the phenolic fractions exhibited mutagen specificity against direct-acting mutagens, being effective in suppressing the frameshift mutagen NPD but failing to inhibit sodium azide (base pair substitution)-induced his+ revertants. ET-1 fraction triterpenoid diglycoside showed a marked effect against sodium azide but was ineffective against NPD. In the case of the indirect-acting mutagen 2AF, all the fractions were found to be quite potent in modulating its mutagenicity in both TA98 and TA100 tester strains of Salmonella typhimurium. The results indicate that the bark of T. arjuna harbors constituents with promising antimutagenic/anticarcinogenic potential that should be investigated further.
{"title":"Antimutagenic potential of extracts isolated from Terminalia arjuna.","authors":"S. Kaur, I. S. Grover, S. Kumar","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.20","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.20","url":null,"abstract":"Terminalia arjuna is an important medicinal plants widely used in the preparation of Ayurvedic formulations used against several ailments. The present investigation was aimed at the fractionation of crude extracts from the bark of T. arjuna in order to isolate and purify the antimutagenic factors present. The antimutagenicity assay was performed to check the modulatory effect of these fractions against NPD, sodium azide, and 2AF, using the Ames Salmonella his+ reversion assay. Most of the phenolic fractions exhibited mutagen specificity against direct-acting mutagens, being effective in suppressing the frameshift mutagen NPD but failing to inhibit sodium azide (base pair substitution)-induced his+ revertants. ET-1 fraction triterpenoid diglycoside showed a marked effect against sodium azide but was ineffective against NPD. In the case of the indirect-acting mutagen 2AF, all the fractions were found to be quite potent in modulating its mutagenicity in both TA98 and TA100 tester strains of Salmonella typhimurium. The results indicate that the bark of T. arjuna harbors constituents with promising antimutagenic/anticarcinogenic potential that should be investigated further.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"20 1","pages":"9-14"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88021825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.ISUPPL.1.50
G. S. Davis, Chris E. Holmes, L. Pfeiffer, D. Hemenway
Silicosis is characterized by mononuclear cell aggregation with mineral particles and fibrosis. Lymphocytes are abundant in these lesions. We exposed inbred strains of mice to a respirable aerosol of cristobalite silica (70 mg/m3, 5 h/d, 12 d) or shamair. Silicosis evolved over months after exposure. The silica-exposed mice showed the accumulation of lymphocytes in alveolar spaces (seen in bronchoalveolar lavage), in lung parenchymal lesions and nodules, and in enlarged bronchial-associated lymphoid tissues and thoracic lymph nodes. The lung lymphocytes were predominantly CD4+ T cells, but numerous CD8+ T cells, natural killer cells, and CD4- gammadelta-TCR+ T cells were present as well. Interferon-gamma (IFN-gamma) production was upregulated, suggesting a THelper-1-like response in silicosis. In silicotic lung tissue, mRNA transcripts for the macrophage-derived cytokines IL-12 and -18 were increased. IFN-gamma gene-deleted mice (C57Bl/6-Ifngtm1 Ts) exposed to silica developed less extensive silicosis and less lung collagen accumulation than wild-type mice. We hypothesize that there is a reiterative amplification cycle in which macrophages with silica may produce cytokines, such as IL-12 and -18, that attract and activate lymphocytes. These activated lymphocytes may then produce additional mediators that in turn attract and activate an expanded secondary population of macrophages. IFN-gamma would be a likely cause of macrophage activation in this cycle. More work is needed to understand the biological events that lead from the inhaled dust to the scarred lung, and to clarify the role of lymphocytes in this process.
{"title":"Lymphocytes, lymphokines, and silicosis.","authors":"G. S. Davis, Chris E. Holmes, L. Pfeiffer, D. Hemenway","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.ISUPPL.1.50","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.ISUPPL.1.50","url":null,"abstract":"Silicosis is characterized by mononuclear cell aggregation with mineral particles and fibrosis. Lymphocytes are abundant in these lesions. We exposed inbred strains of mice to a respirable aerosol of cristobalite silica (70 mg/m3, 5 h/d, 12 d) or shamair. Silicosis evolved over months after exposure. The silica-exposed mice showed the accumulation of lymphocytes in alveolar spaces (seen in bronchoalveolar lavage), in lung parenchymal lesions and nodules, and in enlarged bronchial-associated lymphoid tissues and thoracic lymph nodes. The lung lymphocytes were predominantly CD4+ T cells, but numerous CD8+ T cells, natural killer cells, and CD4- gammadelta-TCR+ T cells were present as well. Interferon-gamma (IFN-gamma) production was upregulated, suggesting a THelper-1-like response in silicosis. In silicotic lung tissue, mRNA transcripts for the macrophage-derived cytokines IL-12 and -18 were increased. IFN-gamma gene-deleted mice (C57Bl/6-Ifngtm1 Ts) exposed to silica developed less extensive silicosis and less lung collagen accumulation than wild-type mice. We hypothesize that there is a reiterative amplification cycle in which macrophages with silica may produce cytokines, such as IL-12 and -18, that attract and activate lymphocytes. These activated lymphocytes may then produce additional mediators that in turn attract and activate an expanded secondary population of macrophages. IFN-gamma would be a likely cause of macrophage activation in this cycle. More work is needed to understand the biological events that lead from the inhaled dust to the scarred lung, and to clarify the role of lymphocytes in this process.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"9 1","pages":"53-65"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82694709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I3.50
N. Chattopadhyay, Amitava Chatterjee
One of the most important cell surface receptors in tumor development is alphavbeta3. To study the role of the alphavbeta3 integrin receptor in the invasive properties of tumor cells, we used human cervical tumor cells SiHa (cell surface alphavbeta3 integrin receptor-positive) and HeLa cells (cell surface alphavbeta3 integrin receptor-negative). Cell adhesion assay showed that SiHa and HeLa cells can bind very efficiently to extracellular matrix proteins fibronectin, laminin, and collagen IV, but the binding of HeLa cells to vitronectin is very poor compared to that of SiHa cells. Comparative invasion assay demonstrated a much lower invasive potential of HeLa cells than SiHa cells. Cell surface alphav and beta3 integrin receptor subunit assay showed the expression of alphavbeta3 integrin receptor on the SiHa cell surface, whereas the HeLa cell surface lacks functional alphavbeta3 heterodimer. The zymogram demonstrated a higher gelatinase/MMP-2 activity in culture medium, whole cell, and membrane extract of SiHa cells than that in HeLa cells. The alphavbeta3 integrin receptor-associated MMP-2 activity of SiHa and HeLa cells was tested in a comparative zymography that clearly showed very high gelatinase/MMP-2 activity in alphav mAb-immunoprecipitated fraction of SiHa cell (containing alphavbeta3 heterodimer) but not in the alphav mAb-immunoprecipitated fraction of HeLa cell membrane extract (containing only the beta3 subunit). Immunoblot assay of alphav monoclonal antibody-immunoprecipitated alphavbeta3 integrin receptor from SiHa cell membrane extract with MMP-2 monoclonal antibody demonstrated the association of MMP-2 protein with alphavbeta3 integrin receptor. We concluded that alphavbeta3 integrin receptor is one of the most important cell surface molecules regulating the invasive property of cervical tumor cells because of its associated gelatinase/MMP-2 activity. Our findings will contribute to a better understanding of the role of integrin receptors, especially of the alphavbeta3 integrin receptor, in the invasive property of cancer cells and possibly affect future therapeutic approaches to cancer invasion and metastasis.
{"title":"Role of alphavbeta3 integrin receptor in the invasive potential of human cervical cancer (SiHa) cells.","authors":"N. Chattopadhyay, Amitava Chatterjee","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I3.50","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I3.50","url":null,"abstract":"One of the most important cell surface receptors in tumor development is alphavbeta3. To study the role of the alphavbeta3 integrin receptor in the invasive properties of tumor cells, we used human cervical tumor cells SiHa (cell surface alphavbeta3 integrin receptor-positive) and HeLa cells (cell surface alphavbeta3 integrin receptor-negative). Cell adhesion assay showed that SiHa and HeLa cells can bind very efficiently to extracellular matrix proteins fibronectin, laminin, and collagen IV, but the binding of HeLa cells to vitronectin is very poor compared to that of SiHa cells. Comparative invasion assay demonstrated a much lower invasive potential of HeLa cells than SiHa cells. Cell surface alphav and beta3 integrin receptor subunit assay showed the expression of alphavbeta3 integrin receptor on the SiHa cell surface, whereas the HeLa cell surface lacks functional alphavbeta3 heterodimer. The zymogram demonstrated a higher gelatinase/MMP-2 activity in culture medium, whole cell, and membrane extract of SiHa cells than that in HeLa cells. The alphavbeta3 integrin receptor-associated MMP-2 activity of SiHa and HeLa cells was tested in a comparative zymography that clearly showed very high gelatinase/MMP-2 activity in alphav mAb-immunoprecipitated fraction of SiHa cell (containing alphavbeta3 heterodimer) but not in the alphav mAb-immunoprecipitated fraction of HeLa cell membrane extract (containing only the beta3 subunit). Immunoblot assay of alphav monoclonal antibody-immunoprecipitated alphavbeta3 integrin receptor from SiHa cell membrane extract with MMP-2 monoclonal antibody demonstrated the association of MMP-2 protein with alphavbeta3 integrin receptor. We concluded that alphavbeta3 integrin receptor is one of the most important cell surface molecules regulating the invasive property of cervical tumor cells because of its associated gelatinase/MMP-2 activity. Our findings will contribute to a better understanding of the role of integrin receptors, especially of the alphavbeta3 integrin receptor, in the invasive property of cancer cells and possibly affect future therapeutic approaches to cancer invasion and metastasis.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"129 1","pages":"211-21"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79574280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I3.80
N. Ramesh, A. S. Vuayaraghavan, B. Desai, M. Natarajan, P. B. Murthy, K. S. Pillai
The pathogenesis of osteogenic sarcoma is not known. Recently, chronic fluoride exposure has been incriminated as having a possible etiologic role by causing a nonspecific osteoblast proliferation. We were interested in exploring the possible relationship between fluoride bone content and p53 mutations. We analyzed p53 mutations in various exons in tissue of osteosarcoma, and correlated the findings with the bone fluoride levels in Indian patients. We analyzed tissue samples from 20 osteosarcoma patients for possible genetic alterations including mutations, and we assessed the extent of fluoride accumulation in bone. Fragments displaying an altered electrophoretic mobility were confirmed as having mutated sequences. Mutation was observed in samples of two cases (10% incidence). Eighteen samples showed bone fluoride levels between 1000 and 27,000 ppm, whereas the 2 mutated samples showed fluoride levels of 64,000 and 89,000 ppm, respectively. The high levels of bone fluoride levels and the similarity of the mechanisms of action between fluoride-induced DNA damage and chemically-induced p53 mutations lead us to propose that high fluoride bone content might have been one of the major factors causing osteosarcoma.
{"title":"Low levels of p53 mutations in Indian patients with osteosarcoma and the correlation with fluoride levels in bone.","authors":"N. Ramesh, A. S. Vuayaraghavan, B. Desai, M. Natarajan, P. B. Murthy, K. S. Pillai","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I3.80","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I3.80","url":null,"abstract":"The pathogenesis of osteogenic sarcoma is not known. Recently, chronic fluoride exposure has been incriminated as having a possible etiologic role by causing a nonspecific osteoblast proliferation. We were interested in exploring the possible relationship between fluoride bone content and p53 mutations. We analyzed p53 mutations in various exons in tissue of osteosarcoma, and correlated the findings with the bone fluoride levels in Indian patients. We analyzed tissue samples from 20 osteosarcoma patients for possible genetic alterations including mutations, and we assessed the extent of fluoride accumulation in bone. Fragments displaying an altered electrophoretic mobility were confirmed as having mutated sequences. Mutation was observed in samples of two cases (10% incidence). Eighteen samples showed bone fluoride levels between 1000 and 27,000 ppm, whereas the 2 mutated samples showed fluoride levels of 64,000 and 89,000 ppm, respectively. The high levels of bone fluoride levels and the similarity of the mechanisms of action between fluoride-induced DNA damage and chemically-induced p53 mutations lead us to propose that high fluoride bone content might have been one of the major factors causing osteosarcoma.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"56 1","pages":"237-43"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90817935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I3.60
P. O'connor, F. Macnaught, W. H. Butler, D. Cooper, G. Margison, A. Povey
Ivermectin is widely used against parasitic infections in veterinary and human medicine and was found to promote the growth of lesions leading to neoplasia when given continuously in the diet to Wistar rats receiving a single low dose of N-methyl-N1-nitro-N-nitrosoguanidine (MNNG). No tumors or pathological lesions were observed in the forestomach of the control animals or those given ivermectin alone. However, compared to animals receiving MNNG alone, rats maintained on a diet containing ivermectin (2 ppm) and given MNNG (12.5 mg/kg) by gavage showed an increased number of neoplasms (9/26 vs 3/18; p = 0.30) and a statistically significant fourfold increase in the number of pathological lesions (18/26 vs 3/18; p = 0.002), which include preneoplasia in the forestomach. In all cases, the pathological lesions were more severe in the animals receiving ivermectin and MNNG, compared to those receiving MNNG alone.
伊维菌素在兽药和人用药中广泛用于抗寄生虫感染，研究发现，如果Wistar大鼠接受单次低剂量n -甲基-n -硝基-n -亚硝基胍(MNNG)，持续在饮食中给予伊维菌素可促进病变生长，导致肿瘤形成。对照组和单独给予伊维菌素组的前胃未见肿瘤和病理病变。然而，与单独接受MNNG的动物相比，维持含有伊维菌素(2 ppm)的饮食并通过灌胃给予MNNG (12.5 mg/kg)的大鼠显示肿瘤数量增加(9/26 vs 3/18;P = 0.30)，病理病变数量增加了4倍(18/26 vs 3/18;P = 0.002)，包括前胃的瘤前病变。在所有病例中，接受伊维菌素和MNNG治疗的动物的病理病变比单独接受MNNG治疗的动物更严重。
{"title":"Increased pathology incidence in the forestomach of rats maintained on a diet containing ivermectin and given a single dose of N-methyl-N1-nitro-N-nitrosoguanidine.","authors":"P. O'connor, F. Macnaught, W. H. Butler, D. Cooper, G. Margison, A. Povey","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I3.60","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I3.60","url":null,"abstract":"Ivermectin is widely used against parasitic infections in veterinary and human medicine and was found to promote the growth of lesions leading to neoplasia when given continuously in the diet to Wistar rats receiving a single low dose of N-methyl-N1-nitro-N-nitrosoguanidine (MNNG). No tumors or pathological lesions were observed in the forestomach of the control animals or those given ivermectin alone. However, compared to animals receiving MNNG alone, rats maintained on a diet containing ivermectin (2 ppm) and given MNNG (12.5 mg/kg) by gavage showed an increased number of neoplasms (9/26 vs 3/18; p = 0.30) and a statistically significant fourfold increase in the number of pathological lesions (18/26 vs 3/18; p = 0.002), which include preneoplasia in the forestomach. In all cases, the pathological lesions were more severe in the animals receiving ivermectin and MNNG, compared to those receiving MNNG alone.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"24 1","pages":"223-7"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79416673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.ISUPPL.1.30
J. Carter, K. Driscoll
To gain a better understanding of the complex mechanisms at work in silica-induced lung disease, we conducted studies comparing the rat and hamster response to silica (alpha-quartz). It has been hypothesized that the rat lung response to low-solubility particles, such as silica, may be due to the recruitment, activation, and subsequent release of damaging mediators by the inflammatory cells. Studies have suggested that hamsters and mice may be less sensitive to the inflammatory and tumorigenic effects of these low-solubility particles than rats. Differences in defense mechanisms, such as antioxidant levels or repair mechanisms, may play a key role in how different species respond to these particles. To investigate species differences in silica-induced lung response, this study compared the effects of alpha-quartz on rats and hamsters. Briefly, rats and hamsters were intratracheally instilled with saline or 0.2, 2, or 20 mg of alpha-quartz. Seven days after exposure, bronchoalveolar lavage (BAL) was performed, and the BAL fluid was evaluated for cell number, type, and LDH. In addition, lung tissue was evaluated for the expression of various pro- and anti-inflammatory mediators. Both species showed dose-related increases in neutrophils and LDH after alpha-quartz exposure; however, the changes were significantly greater in the rat, and rats showed greater expression of several pro-inflammatory mediators and lower levels of the anti-inflammatory mediators. These differences in pro- and anti-inflammatory mediators may contribute to the apparent species differences in tumor response. A basic understanding of the different responses of various species to these inhaled toxins will contribute to our understanding of the mechanisms involved in human disease.
{"title":"The role of inflammation, oxidative stress, and proliferation in silica-induced lung disease: a species comparison.","authors":"J. Carter, K. Driscoll","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.ISUPPL.1.30","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.ISUPPL.1.30","url":null,"abstract":"To gain a better understanding of the complex mechanisms at work in silica-induced lung disease, we conducted studies comparing the rat and hamster response to silica (alpha-quartz). It has been hypothesized that the rat lung response to low-solubility particles, such as silica, may be due to the recruitment, activation, and subsequent release of damaging mediators by the inflammatory cells. Studies have suggested that hamsters and mice may be less sensitive to the inflammatory and tumorigenic effects of these low-solubility particles than rats. Differences in defense mechanisms, such as antioxidant levels or repair mechanisms, may play a key role in how different species respond to these particles. To investigate species differences in silica-induced lung response, this study compared the effects of alpha-quartz on rats and hamsters. Briefly, rats and hamsters were intratracheally instilled with saline or 0.2, 2, or 20 mg of alpha-quartz. Seven days after exposure, bronchoalveolar lavage (BAL) was performed, and the BAL fluid was evaluated for cell number, type, and LDH. In addition, lung tissue was evaluated for the expression of various pro- and anti-inflammatory mediators. Both species showed dose-related increases in neutrophils and LDH after alpha-quartz exposure; however, the changes were significantly greater in the rat, and rats showed greater expression of several pro-inflammatory mediators and lower levels of the anti-inflammatory mediators. These differences in pro- and anti-inflammatory mediators may contribute to the apparent species differences in tumor response. A basic understanding of the different responses of various species to these inhaled toxins will contribute to our understanding of the mechanisms involved in human disease.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"15 1","pages":"33-43"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81794404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.70
K. Anjaria, B. Rao
Caffeine is an environmental agent to which people are commonly exposed through medicines, drinks, food items, etc. It has been shown to be mutagenic in a number of test systems. In addition, it has also been shown to modify the mutagenic response of ionizing radiation, UV, and several chemical mutagens in a number of test systems. We have studied the effect of caffeine on gamma radiation and 4-Nitroquinoline 1-oxide (4-NQO)-induced gene conversion in the yeast Saccharomyces cerevisiae D7. Stationary phase cells were either exposed to 100-600 Gy of 60Co gamma radiation or treated with 0.15-0.3 microM 4-NQO (30 degrees C, 1 hour), after which they were plated on synthetic complete or minimal media with or without caffeine. Caffeine concentrations ranged from 5 to 15 mM. The results indicated that caffeine at 5 and 10 mM decreased gamma radiation-induced gene conversion frequencies significantly at 400 and 600 Gy. At 600 Gy, the decrease was about 30% and 50% with caffeine concentrations of 5 and 10 mM, respectively. In contrast, caffeine was found to increase the induced gene conversion frequency when cells treated with 0.15, 0.225, and 0.3 microM 4-NQO were plated on media containing caffeine. The increase with 5, 10, and 15 mM caffeine was approximately 1.5, 2, and 2.5, respectively, times the value of 4-NQO alone. The results indicate that the posttreatment repair processes following gamma irradiation or 4-NQO treatment are modified via different pathways.
{"title":"Effect of caffeine on the genotoxic effects of gamma radiation and 4-NQO in diploid yeast.","authors":"K. Anjaria, B. Rao","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.70","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.70","url":null,"abstract":"Caffeine is an environmental agent to which people are commonly exposed through medicines, drinks, food items, etc. It has been shown to be mutagenic in a number of test systems. In addition, it has also been shown to modify the mutagenic response of ionizing radiation, UV, and several chemical mutagens in a number of test systems. We have studied the effect of caffeine on gamma radiation and 4-Nitroquinoline 1-oxide (4-NQO)-induced gene conversion in the yeast Saccharomyces cerevisiae D7. Stationary phase cells were either exposed to 100-600 Gy of 60Co gamma radiation or treated with 0.15-0.3 microM 4-NQO (30 degrees C, 1 hour), after which they were plated on synthetic complete or minimal media with or without caffeine. Caffeine concentrations ranged from 5 to 15 mM. The results indicated that caffeine at 5 and 10 mM decreased gamma radiation-induced gene conversion frequencies significantly at 400 and 600 Gy. At 600 Gy, the decrease was about 30% and 50% with caffeine concentrations of 5 and 10 mM, respectively. In contrast, caffeine was found to increase the induced gene conversion frequency when cells treated with 0.15, 0.225, and 0.3 microM 4-NQO were plated on media containing caffeine. The increase with 5, 10, and 15 mM caffeine was approximately 1.5, 2, and 2.5, respectively, times the value of 4-NQO alone. The results indicate that the posttreatment repair processes following gamma irradiation or 4-NQO treatment are modified via different pathways.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"76 1","pages":"39-45"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82978895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.50
R. Balsara, V. Joshi
We have previously reported on cloning a DNA repair gene designated as uvr3 by virtue of its ability to phenotypically complement the UV sensitivity of mutant strain MBH3. Subsequently, we identified the uvr3 gene to be the uvrA gene (gene identification number HI0249) of Haemophilus influenzae Rd. The uvrA gene is a component of the UvrABC excision repair pathway. We studied molecular basis of the UV sensitivity of the MBH3 strain and identified a G-->A transition at nucleotide position 2700 of the uvrA gene, altering the Trp-900 codon (TGG) to a nonsense codon (TGA). Thus, the UvrA protein produced in the mutant strain MBH3 is likely to be truncated and unable to carry out the UV-induced DNA repair, thereby rendering the strain UV sensitive.
{"title":"Molecular basis of UV-sensitive mutant strain MBH3 of Haemophilus influenzae Rd: identification of mutation in the uvrA gene.","authors":"R. Balsara, V. Joshi","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.50","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.50","url":null,"abstract":"We have previously reported on cloning a DNA repair gene designated as uvr3 by virtue of its ability to phenotypically complement the UV sensitivity of mutant strain MBH3. Subsequently, we identified the uvr3 gene to be the uvrA gene (gene identification number HI0249) of Haemophilus influenzae Rd. The uvrA gene is a component of the UvrABC excision repair pathway. We studied molecular basis of the UV sensitivity of the MBH3 strain and identified a G-->A transition at nucleotide position 2700 of the uvrA gene, altering the Trp-900 codon (TGG) to a nonsense codon (TGA). Thus, the UvrA protein produced in the mutant strain MBH3 is likely to be truncated and unable to carry out the UV-induced DNA repair, thereby rendering the strain UV sensitive.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"24 1","pages":"27-32"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85918777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.100
R. Thapliyal, S. S. Deshpande, G.B Maru
Turmeric and/or its main coloring component, curcumin (diferuloylmethane), have been shown to inhibit benzo(a)pyrene [B(a)P]-induced forestomach papillomas in mice. However, the mechanisms of turmeric-mediated chemoprevention are not well understood. To study the mechanisms of turmeric-mediated chemoprevention, we investigated the effects of turmeric feeding on the activities of isozymes of cytochrome P-450 (CYP450)--namely, ethoxyresorufin O-deethylase (EROD, CYP1A1) and methoxyresorufin O-demethylase (MROD, CYP1A2)--which are predominantly involved in the metabolism of B(a)P. We determined the activities of EROD and MROD by monitoring the formation of resorufin from respective substrates in the presence of microsomal proteins obtained from tissues of control, 1% turmeric, 1 mg B(a)P, and 1% turmeric + 1 mg B(a)P-fed Swiss mice. The results indicate that the administration of turmeric through diet significantly inhibited the activities of both EROD and MROD in forestomach (target organ), liver, and lung. In vitro studies employing curcumin, demethoxycurcumin, and bis-demethoxycurcumin suggest that curcumins are the inhibitors in turmeric. Inhibition of B(a)P metabolizing phase I enzymes (EROD, MROD) may be at least in part one of the possible modes of chemopreventive action of turmeric/curcumin.
{"title":"Effects of turmeric on the activities of benzo(a)pyrene-induced cytochrome P-450 isozymes.","authors":"R. Thapliyal, S. S. Deshpande, G.B Maru","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.100","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I1.100","url":null,"abstract":"Turmeric and/or its main coloring component, curcumin (diferuloylmethane), have been shown to inhibit benzo(a)pyrene [B(a)P]-induced forestomach papillomas in mice. However, the mechanisms of turmeric-mediated chemoprevention are not well understood. To study the mechanisms of turmeric-mediated chemoprevention, we investigated the effects of turmeric feeding on the activities of isozymes of cytochrome P-450 (CYP450)--namely, ethoxyresorufin O-deethylase (EROD, CYP1A1) and methoxyresorufin O-demethylase (MROD, CYP1A2)--which are predominantly involved in the metabolism of B(a)P. We determined the activities of EROD and MROD by monitoring the formation of resorufin from respective substrates in the presence of microsomal proteins obtained from tissues of control, 1% turmeric, 1 mg B(a)P, and 1% turmeric + 1 mg B(a)P-fed Swiss mice. The results indicate that the administration of turmeric through diet significantly inhibited the activities of both EROD and MROD in forestomach (target organ), liver, and lung. In vitro studies employing curcumin, demethoxycurcumin, and bis-demethoxycurcumin suggest that curcumins are the inhibitors in turmeric. Inhibition of B(a)P metabolizing phase I enzymes (EROD, MROD) may be at least in part one of the possible modes of chemopreventive action of turmeric/curcumin.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"8 1","pages":"59-63"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81192030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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