Anticarcinogenic potential of tenuazonic acid (TA), a mycotoxin isolated from a fungus, Alternaria alternata, on skin tumorigenesis induced by 7,12-dimethyl benz(a) antracene (DMBA) was investigated. Female Swiss albino mice were exposed topically to 100 nmole of DMBA twice weekly for 20 weeks. Another group of animals was treated with 250 microg TA in acetone daily for a period of 1 week, followed by the same dose of TA prior to every application of DMBA. At the end of 14 weeks, all the animals in the group that was exposed to DMBA alone developed tumors, while 40% of the animals in TA-treated group were found to be tumor free. After 20 weeks, there was no further increase in the number of tumor-bearing animals. Results indicated that prior application of TA significantly delayed the onset of tumorigenesis and also reduced the cumulative number of tumors per tumor-bearing animals. The present studies reveal the antitumor and protective potential of TA against polycyclic aromatic hydrocarbon induced skin carcinogenesis.
{"title":"Protective effect of tenuazonic acid against dimethyl benz(a)antracene-induced skin carcinogenesis in mice.","authors":"M. Antony, Y. Shukla, K. Janardhanan","doi":"10.1002/TCM.10032","DOIUrl":"https://doi.org/10.1002/TCM.10032","url":null,"abstract":"Anticarcinogenic potential of tenuazonic acid (TA), a mycotoxin isolated from a fungus, Alternaria alternata, on skin tumorigenesis induced by 7,12-dimethyl benz(a) antracene (DMBA) was investigated. Female Swiss albino mice were exposed topically to 100 nmole of DMBA twice weekly for 20 weeks. Another group of animals was treated with 250 microg TA in acetone daily for a period of 1 week, followed by the same dose of TA prior to every application of DMBA. At the end of 14 weeks, all the animals in the group that was exposed to DMBA alone developed tumors, while 40% of the animals in TA-treated group were found to be tumor free. After 20 weeks, there was no further increase in the number of tumor-bearing animals. Results indicated that prior application of TA significantly delayed the onset of tumorigenesis and also reduced the cumulative number of tumors per tumor-bearing animals. The present studies reveal the antitumor and protective potential of TA against polycyclic aromatic hydrocarbon induced skin carcinogenesis.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"44 1","pages":"309-14"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75665474","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}
A. P. Bazo, M. A. Rodrigues, J. M. Sforcin, J. D. de Camargo, L. R. Ribeiro, D. Salvadori
Propolis is a honeybee product with several biological and therapeutical properties. Its effect on the process of colon carcinogenesis and DNA damage were evaluated in the male Wistar rats using the aberrant crypt foci (ACF) assay and the comet assay, respectively. For both tests, animals were treated with the colon carcinogen 1,2 dimethylhydrazine (DMH, 40 mg/kg, s.c.) for 2 weeks (two injections/week) in order to induce both DNA damage and ACF. The animals were divided into groups that received propolis (ethanolic extract) at three different doses (10, 30, and 90 mg/kg b.w., by gavage), either simultaneously or after DMH treatment. For the comet assay, peripheral blood samples were collected 4 h after the last DMH treatment. All animals were sacrificed at the 5th week for evaluation of ACF. The results show that only the intermediate dose (30 mg/kg) of propolis, administered after DMH initiation, is significantly associated to a smaller number of aberrant crypts in the distal colon. No effect on DNA damage in peripheral blood cells, however, was verified by the comet assay. These data suggest that propolis has a protective influence on the process of colon carcinogenesis, suppressing the development of preneoplastic lesions, and probably exerts no protection against the initiation of carcinogenesis.
{"title":"Protective action of propolis on the rat colon carcinogenesis.","authors":"A. P. Bazo, M. A. Rodrigues, J. M. Sforcin, J. D. de Camargo, L. R. Ribeiro, D. Salvadori","doi":"10.1002/TCM.10011","DOIUrl":"https://doi.org/10.1002/TCM.10011","url":null,"abstract":"Propolis is a honeybee product with several biological and therapeutical properties. Its effect on the process of colon carcinogenesis and DNA damage were evaluated in the male Wistar rats using the aberrant crypt foci (ACF) assay and the comet assay, respectively. For both tests, animals were treated with the colon carcinogen 1,2 dimethylhydrazine (DMH, 40 mg/kg, s.c.) for 2 weeks (two injections/week) in order to induce both DNA damage and ACF. The animals were divided into groups that received propolis (ethanolic extract) at three different doses (10, 30, and 90 mg/kg b.w., by gavage), either simultaneously or after DMH treatment. For the comet assay, peripheral blood samples were collected 4 h after the last DMH treatment. All animals were sacrificed at the 5th week for evaluation of ACF. The results show that only the intermediate dose (30 mg/kg) of propolis, administered after DMH initiation, is significantly associated to a smaller number of aberrant crypts in the distal colon. No effect on DNA damage in peripheral blood cells, however, was verified by the comet assay. These data suggest that propolis has a protective influence on the process of colon carcinogenesis, suppressing the development of preneoplastic lesions, and probably exerts no protection against the initiation of carcinogenesis.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"53 1","pages":"183-94"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90675301","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}
Increased incidence of mortality and sickness due to cardiopulmonary complications has been associated with elevated levels of urban air particles (UAP), with an aerodynamic diameter of 10 microm (PM 10) and 2.5 microm (PM 2.5). In the present report alternative plant systems and human cells in vitro are associated with human hazard and genotoxic risk assessment of UAP. The genotoxic activities associated with the coarse (PM 10) and the fine fraction (PM 2.5) of airborne particulates have been analyzed by evaluating micronuclei induction and/or sister-chromatid exchange (SCE) using in vitro models of Daucus carota and HS 27 human fibroblast cell suspensions and Zea mays root meristems. Results show variability in the response of the test systems and indicate that the mutagenicity trend in both plant and human cell cultures was directly correlated to the concentration of carbon-rich particles in the fraction of the PM 2.5 airborne particulates. Moreover, in plant tissues, the frequency of micronuclei and SCE was related to an enhancement of the specific activity of the stress-related enzyme peroxidase.
{"title":"Monitoring urban air particulate matter (fractions PM 2.5 and PM 10) genotoxicity by plant systems and human cells in vitro: a comparative analysis.","authors":"A. Poma, L. Arrizza, Pietro Picozzi, L. Spanò","doi":"10.1002/TCM.10020","DOIUrl":"https://doi.org/10.1002/TCM.10020","url":null,"abstract":"Increased incidence of mortality and sickness due to cardiopulmonary complications has been associated with elevated levels of urban air particles (UAP), with an aerodynamic diameter of 10 microm (PM 10) and 2.5 microm (PM 2.5). In the present report alternative plant systems and human cells in vitro are associated with human hazard and genotoxic risk assessment of UAP. The genotoxic activities associated with the coarse (PM 10) and the fine fraction (PM 2.5) of airborne particulates have been analyzed by evaluating micronuclei induction and/or sister-chromatid exchange (SCE) using in vitro models of Daucus carota and HS 27 human fibroblast cell suspensions and Zea mays root meristems. Results show variability in the response of the test systems and indicate that the mutagenicity trend in both plant and human cell cultures was directly correlated to the concentration of carbon-rich particles in the fraction of the PM 2.5 airborne particulates. Moreover, in plant tissues, the frequency of micronuclei and SCE was related to an enhancement of the specific activity of the stress-related enzyme peroxidase.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"41 1","pages":"271-84"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76777832","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}
E. Rencüzoğulları, H. B. Ila, M. Topaktaş, A. Kayraldız, Songuel Budak, M. Arslan
In this study, the chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) were investigated in human lymphocytes treated with spiramycin antibiotic (trade name, rovamycin). Spiramycin did not induce the CAs and SCEs, and also did not decrease the mitotic index (MI). However, spiramycin decreased the replication index (RI) only at 48 h treatment times.
{"title":"No significant increase in chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with spiramycin.","authors":"E. Rencüzoğulları, H. B. Ila, M. Topaktaş, A. Kayraldız, Songuel Budak, M. Arslan","doi":"10.1002/TCM.1038","DOIUrl":"https://doi.org/10.1002/TCM.1038","url":null,"abstract":"In this study, the chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) were investigated in human lymphocytes treated with spiramycin antibiotic (trade name, rovamycin). Spiramycin did not induce the CAs and SCEs, and also did not decrease the mitotic index (MI). However, spiramycin decreased the replication index (RI) only at 48 h treatment times.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"545 1","pages":"51-8"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77736070","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}
C. Gonzalez, O. Nájera, E. Cortés, G. Toledo, L. López, M. Betancourt, R. Ortiz
Infectious disease and malnutrition in children are public health problems in developing countries. Malnutrition is associated with higher levels of DNA damage, and this increased damage could be due to different factors, including the possibility that cells from malnourished children could be more susceptible to environmental damage. The aim of the present study was to evaluate the susceptibility of lymphocytes from malnourished children to DNA damage induced by antibiotics by using the comet assay. The same group of malnourished infected children were studied before and after a treatment period, and compared to a group of well-nourished infected children. Results showed that before and after drug treatment, tail length migration was two times greater in malnourished than in well-nourished children. The proportion of cells with high damage was also increased in malnourished children. Additionally in well-nourished and malnourished children, a cell subpopulation (non-damaged cells) more resistant to DNA damage induced by antibiotics was observed; this was more prevalent in the well-nourished children. Meanwhile, in malnourished children, a cell population seems to be more susceptible and reaches higher levels of DNA damage. This might help explain the impaired immune response observed in malnourished children. The increased DNA migration and the increased proportion of cells with higher levels of damage seem to indicate that malnourished children are more susceptible to DNA damage induced by drugs.
{"title":"Susceptibility to DNA damage induced by antibiotics in lymphocytes from malnourished children.","authors":"C. Gonzalez, O. Nájera, E. Cortés, G. Toledo, L. López, M. Betancourt, R. Ortiz","doi":"10.1002/TCM.10007","DOIUrl":"https://doi.org/10.1002/TCM.10007","url":null,"abstract":"Infectious disease and malnutrition in children are public health problems in developing countries. Malnutrition is associated with higher levels of DNA damage, and this increased damage could be due to different factors, including the possibility that cells from malnourished children could be more susceptible to environmental damage. The aim of the present study was to evaluate the susceptibility of lymphocytes from malnourished children to DNA damage induced by antibiotics by using the comet assay. The same group of malnourished infected children were studied before and after a treatment period, and compared to a group of well-nourished infected children. Results showed that before and after drug treatment, tail length migration was two times greater in malnourished than in well-nourished children. The proportion of cells with high damage was also increased in malnourished children. Additionally in well-nourished and malnourished children, a cell subpopulation (non-damaged cells) more resistant to DNA damage induced by antibiotics was observed; this was more prevalent in the well-nourished children. Meanwhile, in malnourished children, a cell population seems to be more susceptible and reaches higher levels of DNA damage. This might help explain the impaired immune response observed in malnourished children. The increased DNA migration and the increased proportion of cells with higher levels of damage seem to indicate that malnourished children are more susceptible to DNA damage induced by drugs.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"41 1","pages":"147-58"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82925268","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}
M. J. Silva, A. Dias, A. Barreta, P. Nogueira, N.A.A. Castelo-Branco, M. Boavida
Chronic exposure to low frequency (LF) noise and whole-body vibration (WBV) induces both physiological and psychological alterations in man. Recently, we have shown that long-term occupational exposure to LF noise and WBV produces genotoxic effects in man expressed as an increase in sister chromatid exchange (SCE) levels in lymphocytes. The objectives of the present study were to investigate whether the observed effect could be reproduced in a murine model and, if so, which of the agents, LF noise alone or in combination with WBV, would be instrumental in the SCE induction. SCEs were analyzed in spleen lymphocytes of mice exposed to LF noise alone and in combination with WBV for 300 and 600 hr. An effect at the cell cycle kinetics level was also investigated. The results revealed significant increases in the mean SCE number per cell and in the proportion of cells with high frequency of SCEs (HFCs) in lymphocytes of mice submitted to combined noise and WBV over controls. No significant differences were found between single noise-exposed and control mice. A cell cycle delay was observed exclusively in the noise and WBV exposure groups. In conclusion, we demonstrated that, as in exposed workers, prolonged exposure to the combination of LF noise and WBV determines an increase in SCE level in mice while LF noise alone is not effective in SCE induction.
{"title":"Low frequency noise and whole-body vibration cause increased levels of sister chromatid exchange in splenocytes of exposed mice.","authors":"M. J. Silva, A. Dias, A. Barreta, P. Nogueira, N.A.A. Castelo-Branco, M. Boavida","doi":"10.1002/TCM.10012","DOIUrl":"https://doi.org/10.1002/TCM.10012","url":null,"abstract":"Chronic exposure to low frequency (LF) noise and whole-body vibration (WBV) induces both physiological and psychological alterations in man. Recently, we have shown that long-term occupational exposure to LF noise and WBV produces genotoxic effects in man expressed as an increase in sister chromatid exchange (SCE) levels in lymphocytes. The objectives of the present study were to investigate whether the observed effect could be reproduced in a murine model and, if so, which of the agents, LF noise alone or in combination with WBV, would be instrumental in the SCE induction. SCEs were analyzed in spleen lymphocytes of mice exposed to LF noise alone and in combination with WBV for 300 and 600 hr. An effect at the cell cycle kinetics level was also investigated. The results revealed significant increases in the mean SCE number per cell and in the proportion of cells with high frequency of SCEs (HFCs) in lymphocytes of mice submitted to combined noise and WBV over controls. No significant differences were found between single noise-exposed and control mice. A cell cycle delay was observed exclusively in the noise and WBV exposure groups. In conclusion, we demonstrated that, as in exposed workers, prolonged exposure to the combination of LF noise and WBV determines an increase in SCE level in mice while LF noise alone is not effective in SCE induction.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"8 1","pages":"195-203"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85994702","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}
Methanolic extract of Phyllanthus amarus was tested for its anti-mutagenic activity in Salmonella typhimurium strains TA1535, TA100, and TA102 (Ames test). P. amarus extract was able to inhibit the activation and mutagenicity of 2-acetaminofluorene (2-AAF) and aflatoxinB(1) at concentrations of 0.25-2 mg/plate. It was also found to inhibit mutagenicity induced by direct acting mutagens sodium azide (NaN(3)), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), and 4-nitro-0-phenylenediamine (NPD), at concentrations of 1 mg to 0.25 mg/plate. Urinary mutagenicity produced in rats by benzo[a] pyrene was found to be significantly inhibited by the oral administration of Phyllanthus extract. These results indicate significant anti-mutagenicity of the extract in vitro as well as in vivo.
{"title":"Anti-mutagenic activity of Phyllanthus amarus Schum & Thonn in vitro as well as in vivo.","authors":"K. Raphael, T. A. Ajith, S. Joseph, R. Kuttan","doi":"10.1002/TCM.10021","DOIUrl":"https://doi.org/10.1002/TCM.10021","url":null,"abstract":"Methanolic extract of Phyllanthus amarus was tested for its anti-mutagenic activity in Salmonella typhimurium strains TA1535, TA100, and TA102 (Ames test). P. amarus extract was able to inhibit the activation and mutagenicity of 2-acetaminofluorene (2-AAF) and aflatoxinB(1) at concentrations of 0.25-2 mg/plate. It was also found to inhibit mutagenicity induced by direct acting mutagens sodium azide (NaN(3)), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), and 4-nitro-0-phenylenediamine (NPD), at concentrations of 1 mg to 0.25 mg/plate. Urinary mutagenicity produced in rats by benzo[a] pyrene was found to be significantly inhibited by the oral administration of Phyllanthus extract. These results indicate significant anti-mutagenicity of the extract in vitro as well as in vivo.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"1 1","pages":"285-91"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83186245","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}
The frequencies of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) were determined in peripheral blood lymphocyte cultures from women with breast cancer treated by chemotherapy (CT) with FEC (5-fluorouracil, epirubicin, and cyclophosphamide) or CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) cocktail in six CT cycles. The number of patients in each CT cycle were from 1 to 3 for SCE and 2 to 5 for CA. Samples were collected before and 48 h after CT. Although the size of the sample was limited and interindividual variability was wide, it appears that a 21-day interval between CT sessions is sufficient for cell recovery. This fact was demonstrated by the reduction in CA and SCE frequencies between cycles in parallel with the unchanged mitotic index and proliferative index values.
{"title":"Study of chromosome damage in patients with breast cancer treated by two antineoplastic treatments.","authors":"L. M. Silva, C. Takahashi, H. Carrara","doi":"10.1002/TCM.10019","DOIUrl":"https://doi.org/10.1002/TCM.10019","url":null,"abstract":"The frequencies of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) were determined in peripheral blood lymphocyte cultures from women with breast cancer treated by chemotherapy (CT) with FEC (5-fluorouracil, epirubicin, and cyclophosphamide) or CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) cocktail in six CT cycles. The number of patients in each CT cycle were from 1 to 3 for SCE and 2 to 5 for CA. Samples were collected before and 48 h after CT. Although the size of the sample was limited and interindividual variability was wide, it appears that a 21-day interval between CT sessions is sufficient for cell recovery. This fact was demonstrated by the reduction in CA and SCE frequencies between cycles in parallel with the unchanged mitotic index and proliferative index values.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"24 1","pages":"257-69"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91134951","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}
Reproductive toxicology is concerned with chemical or physical agents interfering with fertility in both gender. Adverse effects may be induced directly, especially in adult males by damaging the semen producing epithelium (e.g., DBCP), or indirectly, predominantly by interfering with sex hormonal homeostasis. Many critical events must occur during well-defined periods of prenatal and early postnatal development of the reproductive system. Most of such differentiation processes, several of which in the male critically depend on inducing influences of androgens, cannot take place at later stages, and lack of "imprinting" will result in irreversible defects or dysfunctions. These processes might be disturbed by interfering agents (e.g., by anti-androgens: feminization), provided that the exposure is high enough. Several of the processes known to be essential for male development can also be altered in females by exposure to a large excess of androgens (masculinization). Essential processes required for normal male development include: 1) androgen-dependent differentiation of the male phenotype during late embryonic development, 2) differentiation of the male secondary sex organs during the fetal period, 3) formation of a fixed number of Sertoli cells during the perinatal period, 4) imprinting of male sexual behavior in defined brain areas during the perinatal period, 5) imprinting of the pulsatile GnRH regulation of hypophysial hormone formation in both gender via the hypothalamico-hypophysial axis, and 6) differentiation of the male organism during puberty. Many effects on fertility can be induced on the adult organism. Besides a direct action on the receptors, inhibition of the feed back mechanism that guarantees sex hormonal homeostasis is another mode of action. Many synthetic steroid compounds exhibit effects on more than one receptor, thus causing a complex situation. This must also be taken into account when analyzing possible effects of "ecohormones." Adverse hormonal actions are well established from experience in clinical and experimental medicine, using either natural or synthetic sex hormones, or enzyme inhibitors. Possible effects of "environmental" agents either mimicking or inhibiting sex hormonal actions are less well studied in clinical trials. Because of considerable species differences in hormonal effects, especially in pharmacokinetics, data of animal studies are of limited predictive value for extrapolations in preventive hazard minimization (but may be useful for revealing possible mechanisms of action). Data of in-vitro studies are even less suitable for extrapolations. It may be doubted that exposure of the general population to "ecohormones" or "xenohormones" is sufficient to induce clear-cut clinical effects. Adverse effects induced by, e.g., greatly unbalanced diets or after accidental overdoses cannot be excluded.
{"title":"Reproductive toxicology: the science today.","authors":"D. Neubert","doi":"10.1002/TCM.10017","DOIUrl":"https://doi.org/10.1002/TCM.10017","url":null,"abstract":"Reproductive toxicology is concerned with chemical or physical agents interfering with fertility in both gender. Adverse effects may be induced directly, especially in adult males by damaging the semen producing epithelium (e.g., DBCP), or indirectly, predominantly by interfering with sex hormonal homeostasis. Many critical events must occur during well-defined periods of prenatal and early postnatal development of the reproductive system. Most of such differentiation processes, several of which in the male critically depend on inducing influences of androgens, cannot take place at later stages, and lack of \"imprinting\" will result in irreversible defects or dysfunctions. These processes might be disturbed by interfering agents (e.g., by anti-androgens: feminization), provided that the exposure is high enough. Several of the processes known to be essential for male development can also be altered in females by exposure to a large excess of androgens (masculinization). Essential processes required for normal male development include: 1) androgen-dependent differentiation of the male phenotype during late embryonic development, 2) differentiation of the male secondary sex organs during the fetal period, 3) formation of a fixed number of Sertoli cells during the perinatal period, 4) imprinting of male sexual behavior in defined brain areas during the perinatal period, 5) imprinting of the pulsatile GnRH regulation of hypophysial hormone formation in both gender via the hypothalamico-hypophysial axis, and 6) differentiation of the male organism during puberty. Many effects on fertility can be induced on the adult organism. Besides a direct action on the receptors, inhibition of the feed back mechanism that guarantees sex hormonal homeostasis is another mode of action. Many synthetic steroid compounds exhibit effects on more than one receptor, thus causing a complex situation. This must also be taken into account when analyzing possible effects of \"ecohormones.\" Adverse hormonal actions are well established from experience in clinical and experimental medicine, using either natural or synthetic sex hormones, or enzyme inhibitors. Possible effects of \"environmental\" agents either mimicking or inhibiting sex hormonal actions are less well studied in clinical trials. Because of considerable species differences in hormonal effects, especially in pharmacokinetics, data of animal studies are of limited predictive value for extrapolations in preventive hazard minimization (but may be useful for revealing possible mechanisms of action). Data of in-vitro studies are even less suitable for extrapolations. It may be doubted that exposure of the general population to \"ecohormones\" or \"xenohormones\" is sufficient to induce clear-cut clinical effects. Adverse effects induced by, e.g., greatly unbalanced diets or after accidental overdoses cannot be excluded.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"20 1","pages":"159-74"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83791927","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}
Mirex is a pesticide that is environmentally stable, accumulates in body tissues, and is embryo- and feto-toxic at high concentrations in vivo. This study is the first to evaluate the effects of mirex on organogenesis-stage embryos in vitro. Mouse embryos were exposed on gestation day 8.5 for 24 h in whole-embryo culture to mirex at 100, 200, or 400 microg/ml dissolved in xylene and compared with xylene-treated controls (1, 2, or 4 microl/ml, respectively) and untreated controls. Embryos were evaluated for malformations, somite number, total protein content, and visceral yolk sac circulation. Potential embryotoxic mechanisms were evaluated by using PCNA stain for cell proliferation and the TUNEL assay for apoptotic cell death. Mirex-exposed embryos demonstrated increased malformation rates and decreased total embryonic protein contents at > or =200 microg/ml mirex, and decreased somite numbers and VYS circulation at > or =100 microg/ml mirex, compared with xylene-treated controls. There was no difference in PCNA levels or TUNEL staining in mirex-treated embryos compared with xylene-treated controls or untreated controls. Thus, mirex is embryotoxic in vitro to early organogenesis stage mouse embryos at concentrations > or =100 microg/ml, but the effects do not appear to be mediated by changes in cell proliferation or apoptotic cell death.
{"title":"Embryotoxicity of the pesticide mirex in vitro.","authors":"Ahmed A El-Bayomy, I. Smoak, S. Branch","doi":"10.1002/TCM.10016","DOIUrl":"https://doi.org/10.1002/TCM.10016","url":null,"abstract":"Mirex is a pesticide that is environmentally stable, accumulates in body tissues, and is embryo- and feto-toxic at high concentrations in vivo. This study is the first to evaluate the effects of mirex on organogenesis-stage embryos in vitro. Mouse embryos were exposed on gestation day 8.5 for 24 h in whole-embryo culture to mirex at 100, 200, or 400 microg/ml dissolved in xylene and compared with xylene-treated controls (1, 2, or 4 microl/ml, respectively) and untreated controls. Embryos were evaluated for malformations, somite number, total protein content, and visceral yolk sac circulation. Potential embryotoxic mechanisms were evaluated by using PCNA stain for cell proliferation and the TUNEL assay for apoptotic cell death. Mirex-exposed embryos demonstrated increased malformation rates and decreased total embryonic protein contents at > or =200 microg/ml mirex, and decreased somite numbers and VYS circulation at > or =100 microg/ml mirex, compared with xylene-treated controls. There was no difference in PCNA levels or TUNEL staining in mirex-treated embryos compared with xylene-treated controls or untreated controls. Thus, mirex is embryotoxic in vitro to early organogenesis stage mouse embryos at concentrations > or =100 microg/ml, but the effects do not appear to be mediated by changes in cell proliferation or apoptotic cell death.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"116 1","pages":"239-49"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88083850","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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