To the Editor: In my latter days (I'm being falsely modest of course), I am resorting to writing persnickety reviews and not surprisingly being ignored, misquoted or misunderstood. I think the last is worst. An example of which occurs in the article by Fein et al., [1] in Teratogenesis, Carcinogenesis and Mutagenesis. This arcane missive gets it wrong from the first sentence of the abstract, where the assertion is made that early embryonic death and malformations are among "the complications" of diabetic pregnancy. Whether inadvertantly or otherwise it is unstated whether this asservation refers to humans or to other animals.
致编辑:在我最后的日子里(当然，我是在假装谦虚)，我开始写一些吹毛求疵的评论，毫无疑问，这些评论会被忽视、错误引用或误解。我认为最后一种是最糟糕的。Fein等人[1]在Teratogenesis, carcingenesis and Mutagenesis的文章中就有一个例子。这封晦涩难懂的信函从摘要的第一句话就错了，摘要断言早期胚胎死亡和畸形是糖尿病妊娠的“并发症”之一。无论是无意还是无意，都没有说明这种保护是指人类还是指其他动物。
{"title":"Re: Diabetes teratogenicity in mice is accompanied with distorted expression of TGF‐β2 in the uterus. Fein et al. 2001;22:59–71.","authors":"H. Kalter","doi":"10.1002/TCM.10022","DOIUrl":"https://doi.org/10.1002/TCM.10022","url":null,"abstract":"To the Editor: In my latter days (I'm being falsely modest of course), I am resorting to writing persnickety reviews and not surprisingly being ignored, misquoted or misunderstood. I think the last is worst. An example of which occurs in the article by Fein et al., [1] in Teratogenesis, Carcinogenesis and Mutagenesis. This arcane missive gets it wrong from the first sentence of the abstract, where the assertion is made that early embryonic death and malformations are among \"the complications\" of diabetic pregnancy. Whether inadvertantly or otherwise it is unstated whether this asservation refers to humans or to other animals.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"154 1","pages":"235-236"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85808717","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}
J. Błasiak, Magdalena Kadłubek, J. Kowalik, H. Romanowicz‐Makowska, T. Pertyński
Telomerase activation can be considered as a critical step in cell immortalization. The enzyme elongates or maintains telomere length by adding to its end tandem TTAGGG repeats by using its endogenous RNA template. Telomerase is not detectable in most somatic cells but is upregulated in germ line cells and in 85-90% of human cancers, which suggests important role of telomerase in neoplastic transformation. Consequently, telomerase has been proposed as a potentially highly selective target for the development of antiproliferative agents. Platinum complexes are widely administrated in cancer therapy. A conjugate of selenite with diammineplatinum [(NH(3))(2)Pt(SeO(3))(2)] is a novel potential anticancer drug. Using alkaline single cell gel electrophoresis (comet assay), we showed that the drug at 5-30 microM induced concentration-dependent damage to DNA of endometrial cancer cells derived from tumor samples. Sodium ascorbate at 10 and 50 microM reduced the extent of the DNA damage evoked by the drug. (NH(3))(2)Pt(SeO(3)) reduced telomerase activity in the cells in a concentration-dependent manner as measured by using the telomere repeat amplification protocol (TRAP) assay. This effect was independent of sodium ascorbate. Therefore, mutagenic effects of the conjugate can be reduced by well-recognized antimutagen, sodium ascorbate, but it can still retain ability to affect neoplastic transformation. The results obtained indicate that (NH(3))(2)Pt(SeO(3)) may specifically inhibit telomerase activity in endometrial cancer cells.
{"title":"Inhibition of telomerase activity in endometrial cancer cells by selenium-cisplatin conjugate despite suppression of its DNA-damaging activity by sodium ascorbate.","authors":"J. Błasiak, Magdalena Kadłubek, J. Kowalik, H. Romanowicz‐Makowska, T. Pertyński","doi":"10.1002/TCM.1040","DOIUrl":"https://doi.org/10.1002/TCM.1040","url":null,"abstract":"Telomerase activation can be considered as a critical step in cell immortalization. The enzyme elongates or maintains telomere length by adding to its end tandem TTAGGG repeats by using its endogenous RNA template. Telomerase is not detectable in most somatic cells but is upregulated in germ line cells and in 85-90% of human cancers, which suggests important role of telomerase in neoplastic transformation. Consequently, telomerase has been proposed as a potentially highly selective target for the development of antiproliferative agents. Platinum complexes are widely administrated in cancer therapy. A conjugate of selenite with diammineplatinum [(NH(3))(2)Pt(SeO(3))(2)] is a novel potential anticancer drug. Using alkaline single cell gel electrophoresis (comet assay), we showed that the drug at 5-30 microM induced concentration-dependent damage to DNA of endometrial cancer cells derived from tumor samples. Sodium ascorbate at 10 and 50 microM reduced the extent of the DNA damage evoked by the drug. (NH(3))(2)Pt(SeO(3)) reduced telomerase activity in the cells in a concentration-dependent manner as measured by using the telomere repeat amplification protocol (TRAP) assay. This effect was independent of sodium ascorbate. Therefore, mutagenic effects of the conjugate can be reduced by well-recognized antimutagen, sodium ascorbate, but it can still retain ability to affect neoplastic transformation. The results obtained indicate that (NH(3))(2)Pt(SeO(3)) may specifically inhibit telomerase activity in endometrial cancer cells.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"13 1","pages":"73-82"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74193310","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. Fein, N. Magid, H. Carp, V. Toder, A. Torchinsky
To the Editor: Dr. Kalter claims that our assertion "Early embryonic deaths as well as malformed newborns are among complications of the diabetic pregnancy" [1] is wrong, both if it refers to humans or animals. While respecting Dr. Kalter's opinion that, neither experimental nor epidemiological studies prove the teratogenicity of maternal diabetes, we cannot agree.
{"title":"Re: Diabetes teratogenicity in mice is accompanied with distorted expression of TGF-β2 in the uterus. Fein et al. 2001;22:59–71. Response to H. Kalter.","authors":"A. Fein, N. Magid, H. Carp, V. Toder, A. Torchinsky","doi":"10.1002/TCM.10023","DOIUrl":"https://doi.org/10.1002/TCM.10023","url":null,"abstract":"To the Editor: Dr. Kalter claims that our assertion \"Early embryonic deaths as well as malformed newborns are among complications of the diabetic pregnancy\" [1] is wrong, both if it refers to humans or animals. While respecting Dr. Kalter's opinion that, neither experimental nor epidemiological studies prove the teratogenicity of maternal diabetes, we cannot agree.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"1 1","pages":"237-238"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83009950","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}
D-003 is a mixture of very long chain aliphatic acids purified from sugar cane wax, wherein octacosanoic acid represents the major component. Previous experimental studies have shown that D-003 inhibits platelet aggregation in rodents. Also, its lowers total (TC) and low-density lipoprotein cholesterol (LDL-C) in normocholesterolemic rabbits in a dose-dependent manner and inhibits cholesterol biosynthesis in fibroblast cultures. The present study was performed to investigate the in vitro cytotoxic and genotoxic potential effects of D-003 assessed through two tests: the neutral red (NR) assay and the Ames test. Positive and negative controls were included in each experimental series. Compared with controls, no cytotoxicity was evident after 24 and 72 h of treatment with doses up to 1,000 microg/ml in the NR assay. On the other hand, D-003 (5-5,000 microg/plate) did not increase the frequency of reverse mutations in the Ames test in both alternatives with or without S9 mix metabolic activation and a pre-incubation step. The positive control chemicals included in each experiment, namely, treatment with sodium dodecyl sulphate (SDS) in the NR assay and sodium azide (NaAz), 2-aminofluorene (AF), and dimethylnitrosamine (DMNA) in the Ames test, induced the expected changes, such as a decrease in optical density (OD) values in the NR assay and an increase in the frequency of reverse mutations in the Ames test. The present results indicate that D-003 did not show evidence of cytotoxic or genotoxic potential in tests able to detect the ability of chemicals to disrupt cells (NR assay) or to induce gene mutations (Ames test).
{"title":"Preliminary evaluation of the cytotoxic and genotoxic potential of D-003: Mixture of very long chain fatty acids.","authors":"R. Gámez, I. Rodeiro, I. Fernández, P. Acosta","doi":"10.1002/TCM.10001","DOIUrl":"https://doi.org/10.1002/TCM.10001","url":null,"abstract":"D-003 is a mixture of very long chain aliphatic acids purified from sugar cane wax, wherein octacosanoic acid represents the major component. Previous experimental studies have shown that D-003 inhibits platelet aggregation in rodents. Also, its lowers total (TC) and low-density lipoprotein cholesterol (LDL-C) in normocholesterolemic rabbits in a dose-dependent manner and inhibits cholesterol biosynthesis in fibroblast cultures. The present study was performed to investigate the in vitro cytotoxic and genotoxic potential effects of D-003 assessed through two tests: the neutral red (NR) assay and the Ames test. Positive and negative controls were included in each experimental series. Compared with controls, no cytotoxicity was evident after 24 and 72 h of treatment with doses up to 1,000 microg/ml in the NR assay. On the other hand, D-003 (5-5,000 microg/plate) did not increase the frequency of reverse mutations in the Ames test in both alternatives with or without S9 mix metabolic activation and a pre-incubation step. The positive control chemicals included in each experiment, namely, treatment with sodium dodecyl sulphate (SDS) in the NR assay and sodium azide (NaAz), 2-aminofluorene (AF), and dimethylnitrosamine (DMNA) in the Ames test, induced the expected changes, such as a decrease in optical density (OD) values in the NR assay and an increase in the frequency of reverse mutations in the Ames test. The present results indicate that D-003 did not show evidence of cytotoxic or genotoxic potential in tests able to detect the ability of chemicals to disrupt cells (NR assay) or to induce gene mutations (Ames test).","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"19 1","pages":"175-81"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86317391","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}
N. Rocha, L. F. Barbisan, M. L. de Oliveira, J. D. de Camargo
The influences of fasting on DEN-initiation and of intermittent fasting (IF) on the rat liver chemical carcinogenesis process were evaluated in a 52-week long assay. Three groups of adult male Wistar rats were used: Groups 1 to 3 were treated with a single i.p. injection of 200 mg/kg of diethylnitrosamine (DEN). Group 2 was submitted to 48 h fasting prior to DEN treatment. After the 4th week, Group 3 was submitted to IF, established as 48 h weekly fasting during 48 weeks, while Groups 1 and 2 were fed ad libitum until the 52nd week. All animals were submitted to 70% partial hepatectomy and sacrificed at the 3rd and 52nd weeks, respectively. Fasting prior to DEN-initiation did not influence the development of altered foci of hepatocytes (AFHs) and of hepatic nodules (Group 2 vs. Group G1). IF inhibited the development of preneoplastic lesions, since this dietary regimen decreased the number and the size of glutathione S-transferase (GST-P) positive foci and the number and size of liver nodules (Group G3 vs. Group G1). The inhibitory effect of IF was also reflected in the development of clear and basophilic cell foci. These results indicate that long-term IF regimen exerts an anti-promoting effect on rat hepatocarcinogenesis induced by DEN.
{"title":"Effects of fasting and intermittent fasting on rat hepatocarcinogenesis induced by diethylnitrosamine.","authors":"N. Rocha, L. F. Barbisan, M. L. de Oliveira, J. D. de Camargo","doi":"10.1002/TCM.10005","DOIUrl":"https://doi.org/10.1002/TCM.10005","url":null,"abstract":"The influences of fasting on DEN-initiation and of intermittent fasting (IF) on the rat liver chemical carcinogenesis process were evaluated in a 52-week long assay. Three groups of adult male Wistar rats were used: Groups 1 to 3 were treated with a single i.p. injection of 200 mg/kg of diethylnitrosamine (DEN). Group 2 was submitted to 48 h fasting prior to DEN treatment. After the 4th week, Group 3 was submitted to IF, established as 48 h weekly fasting during 48 weeks, while Groups 1 and 2 were fed ad libitum until the 52nd week. All animals were submitted to 70% partial hepatectomy and sacrificed at the 3rd and 52nd weeks, respectively. Fasting prior to DEN-initiation did not influence the development of altered foci of hepatocytes (AFHs) and of hepatic nodules (Group 2 vs. Group G1). IF inhibited the development of preneoplastic lesions, since this dietary regimen decreased the number and the size of glutathione S-transferase (GST-P) positive foci and the number and size of liver nodules (Group G3 vs. Group G1). The inhibitory effect of IF was also reflected in the development of clear and basophilic cell foci. These results indicate that long-term IF regimen exerts an anti-promoting effect on rat hepatocarcinogenesis induced by DEN.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"1 1","pages":"129-38"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90807852","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}
Yahya Kargalioglu, B. McMillan, R. Minear, M. Plewa
We analyzed the cytotoxicity and mutagenicity of the drinking water disinfection by-products (DBPs) bromoform (BF), bromoacetic acid (BA), dibromoacetic acid (DBA), tribromoacetic acid (TCA), chloroform (CF), chloroacetic acid (CA), dichloroacetic acid (DCA), trichloroacetic acid (TCA), 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), and potassium bromate (KBrO3) in Salmonella typhimurium strains TA98, TA100, and RSJ100 +/- S9. Solvent controls of DMSO and ethanol and a positive control of ethylmethanesulfonate (EMS) were also analyzed. We developed a rapid microplate-based method to determine the cytotoxicity of the DBPs and we determined their mutagenic potencies. The distributions of the rank order for the cytotoxicity and mutagenicity of these DBPs were compared and the structure-function relationships were identified. TA100 -S9 was the most sensitive strain for these DBPs. The rank order of the mutagenic potency adjusted with a cytoxicity factor was MX > BA > EMS > DBA > DCA > CA with TBA, TCA, BF, and CF not mutagenic. From a structure-function perspective, the brominated acetic acids were more cytotoxic and mutagenic than their chlorinated analogs. BA was 150x more mutagenic than CA. The mutagenic potency of the haloacetic acids was inversely related to the number of halogen atoms of the molecule. BA was 36x more mutagenic than DBA. The differential cytotoxicity expressed by the DBPs indicated that a cytotoxicity analysis enhanced the sensitivity of the mutagenicity data, which resulted in an enhanced precision for comparing their relative mutagenic strengths. This information is critical when conducting quantitative structure-function analysis of these hazardous agents.
本文对鼠伤寒沙门菌菌株TA98、TA100和RSJ100 +/- S9的饮水消毒副产物(DBPs)溴仿(BF)、溴乙酸(BA)、二溴乙酸(DBA)、三溴乙酸(TCA)、氯仿(CF)、氯乙酸(CA)、二氯乙酸(DCA)、三氯乙酸(TCA)、3-氯-4-(二氯甲基)-5-羟基-2[5H]-呋喃酮(MX)和溴酸钾(KBrO3)的细胞毒性和致突变性进行了分析。同时分析了DMSO和乙醇的溶剂对照和甲磺酸乙酯(EMS)的阳性对照。我们开发了一种基于微孔板的快速方法来测定DBPs的细胞毒性，并测定了它们的致突变能力。比较了这些DBPs的细胞毒性和诱变性的等级分布，并确定了结构-功能关系。TA100 -S9是对这些dbp最敏感的菌株。随细胞毒因子的变化，其致突变性排序为MX > BA > EMS > DBA > DCA > CA, TBA、TCA、BF和CF均不致突变性。从结构-功能的角度来看，溴化乙酸比其氯化类似物具有更强的细胞毒性和诱变性。BA的致突变性是CA的150倍。卤素乙酸的致突变性与分子中卤素原子的数目成反比。BA的致突变性是DBA的36倍。dbp表达的细胞毒性差异表明，细胞毒性分析提高了致突变性数据的敏感性，从而提高了比较它们相对致突变性强度的精度。这些信息在对这些有害物质进行定量结构-功能分析时至关重要。
{"title":"Analysis of the cytotoxicity and mutagenicity of drinking water disinfection by-products in Salmonella typhimurium.","authors":"Yahya Kargalioglu, B. McMillan, R. Minear, M. Plewa","doi":"10.1002/TCM.10010","DOIUrl":"https://doi.org/10.1002/TCM.10010","url":null,"abstract":"We analyzed the cytotoxicity and mutagenicity of the drinking water disinfection by-products (DBPs) bromoform (BF), bromoacetic acid (BA), dibromoacetic acid (DBA), tribromoacetic acid (TCA), chloroform (CF), chloroacetic acid (CA), dichloroacetic acid (DCA), trichloroacetic acid (TCA), 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), and potassium bromate (KBrO3) in Salmonella typhimurium strains TA98, TA100, and RSJ100 +/- S9. Solvent controls of DMSO and ethanol and a positive control of ethylmethanesulfonate (EMS) were also analyzed. We developed a rapid microplate-based method to determine the cytotoxicity of the DBPs and we determined their mutagenic potencies. The distributions of the rank order for the cytotoxicity and mutagenicity of these DBPs were compared and the structure-function relationships were identified. TA100 -S9 was the most sensitive strain for these DBPs. The rank order of the mutagenic potency adjusted with a cytoxicity factor was MX > BA > EMS > DBA > DCA > CA with TBA, TCA, BF, and CF not mutagenic. From a structure-function perspective, the brominated acetic acids were more cytotoxic and mutagenic than their chlorinated analogs. BA was 150x more mutagenic than CA. The mutagenic potency of the haloacetic acids was inversely related to the number of halogen atoms of the molecule. BA was 36x more mutagenic than DBA. The differential cytotoxicity expressed by the DBPs indicated that a cytotoxicity analysis enhanced the sensitivity of the mutagenicity data, which resulted in an enhanced precision for comparing their relative mutagenic strengths. This information is critical when conducting quantitative structure-function analysis of these hazardous agents.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"38 1","pages":"113-28"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91301901","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}
Aqueous extracts of the sporophores of eight mushroom species were assessed for their ability to prevent H2O2-induced oxidative damage to cellular DNA using the single-cell gel electrophoresis ("Comet") assay. The highest genoprotective effects were obtained with cold (20 degrees C) and hot (100 degrees C) water extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies, respectively. No protective effects were observed with Mushroom Derived Preparations (MDPs) from Flammulina velutipes, Auricularia auricula, Hypsizygus marmoreus, Lentinula edodes, Pleurotus sajor-caju, and Volvariella volvacea. These findings indicate that some edible mushrooms represent a valuable source of biologically active compounds with potential for protecting cellular DNA from oxidative damage.
{"title":"Mushroom-derived preparations in the prevention of H2O2-induced oxidative damage to cellular DNA.","authors":"Yu-ling Shi, A. James, I. Benzie, J. Buswell","doi":"10.1002/TCM.10008","DOIUrl":"https://doi.org/10.1002/TCM.10008","url":null,"abstract":"Aqueous extracts of the sporophores of eight mushroom species were assessed for their ability to prevent H2O2-induced oxidative damage to cellular DNA using the single-cell gel electrophoresis (\"Comet\") assay. The highest genoprotective effects were obtained with cold (20 degrees C) and hot (100 degrees C) water extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies, respectively. No protective effects were observed with Mushroom Derived Preparations (MDPs) from Flammulina velutipes, Auricularia auricula, Hypsizygus marmoreus, Lentinula edodes, Pleurotus sajor-caju, and Volvariella volvacea. These findings indicate that some edible mushrooms represent a valuable source of biologically active compounds with potential for protecting cellular DNA from oxidative damage.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"35 1","pages":"103-11"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87182324","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. I. Gómez, E. Valles, S. Fanelli, A. M. de Layño, G. D. Castro, J. Castro
In previous studies from our laboratory we reported the presence in highly purified liver nuclei, free of contamination with other organelles, of an ethanol metabolizing system (NEMS) able to lead to acetaldehyde and 1-hydroxyethyl free radicals (1HEt). In the present study we tested whether this NEMS is inducible by chronic alcohol administration to rats and whether these nuclei also have increased ability to bioactivate N-nitrosodimethylamine (NDMA). Sprague Dawley male rats (125-150g) were fed with a nutritionally adequate liquid diet containing alcohol to provide 36% of total energy (standard Lieber-De Carli rat diet), for 28 days. Controls received an isocaloric diet without alcohol. Animals were sacrificed, livers were excised and microsomes and purified nuclear fractions were prepared. Both microsomes and nuclei from treated animals had significantly increased ability compared to controls, to biotransform ethanol to acetaldehyde using NADPH as cofactor under an air atmosphere. Both organelles also exhibited significantly increased capacity compared to controls, to bioactivate NDMA to formaldehyde and to reactive metabolites that bind covalently to proteins. Nuclear preparations from control animals were also able to metabolize NDMA to formaldehyde and reactive metabolites. Results indicate that liver nuclei may have a CYP2E1 able to bioactivate both NDMA and EtOH and that these processes are being induced by chronic alcohol drinking. The bioactivation of these xenobiotics to reactive metabolites in the neighborhood of nuclear proteins and DNA might have significant toxicological implications.
{"title":"Alcohol induction of liver nuclear ethanol and N-nitrosodimethylamine metabolism to reactive metabolites.","authors":"M. I. Gómez, E. Valles, S. Fanelli, A. M. de Layño, G. D. Castro, J. Castro","doi":"10.1002/TCM.10009","DOIUrl":"https://doi.org/10.1002/TCM.10009","url":null,"abstract":"In previous studies from our laboratory we reported the presence in highly purified liver nuclei, free of contamination with other organelles, of an ethanol metabolizing system (NEMS) able to lead to acetaldehyde and 1-hydroxyethyl free radicals (1HEt). In the present study we tested whether this NEMS is inducible by chronic alcohol administration to rats and whether these nuclei also have increased ability to bioactivate N-nitrosodimethylamine (NDMA). Sprague Dawley male rats (125-150g) were fed with a nutritionally adequate liquid diet containing alcohol to provide 36% of total energy (standard Lieber-De Carli rat diet), for 28 days. Controls received an isocaloric diet without alcohol. Animals were sacrificed, livers were excised and microsomes and purified nuclear fractions were prepared. Both microsomes and nuclei from treated animals had significantly increased ability compared to controls, to biotransform ethanol to acetaldehyde using NADPH as cofactor under an air atmosphere. Both organelles also exhibited significantly increased capacity compared to controls, to bioactivate NDMA to formaldehyde and to reactive metabolites that bind covalently to proteins. Nuclear preparations from control animals were also able to metabolize NDMA to formaldehyde and reactive metabolites. Results indicate that liver nuclei may have a CYP2E1 able to bioactivate both NDMA and EtOH and that these processes are being induced by chronic alcohol drinking. The bioactivation of these xenobiotics to reactive metabolites in the neighborhood of nuclear proteins and DNA might have significant toxicological implications.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"58 1","pages":"139-45"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80716584","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 study examines the relationship between lipid peroxidation, DNA damage, and cell morphology after the exposure of R1 Rhabdomyosarcoma cells to two different dose-rates of gamma rays. Exponential cultures of R1 cells were irradiated with single dose of 5 Gy at high dose rate (0.833 Gy/min) and low dose rate (0.0707 Gy/min). The concentration of two aldehydes, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), were determined. DNA damage induction and repair were measured by using the alkaline version of the comet assay. Cellular alteration was also estimated microscopically as was the frequency of cells with micronuclei and proportion of apoptosis and necrosis. These parameters were evaluated immediately (time 0) and after different times up to 48 h of incubation in 37 degrees C, after irradiation. Results indicate that a low dose rate in comparison to high dose rate caused a significantly higher increase of aldehydes concentration observed at 12 h, followed by obviously higher DNA damage at 48 h and altered cellular morphology. The inverse dose-rate effect estimated for the gamma rays Co-60 source was found to be related to the measured biochemical and morphological parameters.
{"title":"Lipid peroxidation, DNA damage, and cellular morphology of R1 Rhabdomyosarcoma cell line irradiated in vitro by gamma-rays with different dose rates.","authors":"W. Przybyszewski, M. Wideł, O. Palyvoda","doi":"10.1002/TCM.10006","DOIUrl":"https://doi.org/10.1002/TCM.10006","url":null,"abstract":"The study examines the relationship between lipid peroxidation, DNA damage, and cell morphology after the exposure of R1 Rhabdomyosarcoma cells to two different dose-rates of gamma rays. Exponential cultures of R1 cells were irradiated with single dose of 5 Gy at high dose rate (0.833 Gy/min) and low dose rate (0.0707 Gy/min). The concentration of two aldehydes, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), were determined. DNA damage induction and repair were measured by using the alkaline version of the comet assay. Cellular alteration was also estimated microscopically as was the frequency of cells with micronuclei and proportion of apoptosis and necrosis. These parameters were evaluated immediately (time 0) and after different times up to 48 h of incubation in 37 degrees C, after irradiation. Results indicate that a low dose rate in comparison to high dose rate caused a significantly higher increase of aldehydes concentration observed at 12 h, followed by obviously higher DNA damage at 48 h and altered cellular morphology. The inverse dose-rate effect estimated for the gamma rays Co-60 source was found to be related to the measured biochemical and morphological parameters.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"121 1","pages":"93-102"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72702694","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}
J. Sierens, J. Hartley, M. J. Campbell, A. Leathem, J. Woodside
Isoflavones are plant compounds, proposed to have health benefits in a variety of human diseases, including coronary heart disease and endocrine-responsive cancers. Their physiological effects include possible antioxidant activity, therefore suggesting a role for isoflavones in the prevention of male infertility. The aim of this study was to test the antioxidant effects of the isoflavones genistein and equol on sperm DNA integrity, assessed in vitro after hydrogen peroxide-mediated damage, using the comet assay. Pre-treatment with genistein or equol at doses of 0.01-100 micromol/l significantly protected sperm DNA against oxidative damage. Both ascorbic acid (10-600 micromol/l) and alpha-tocopherol (1-100 micromol/l) also protected. Compared with ascorbic acid and alpha-tocopherol, added at physiological concentrations, genistein was the most potent antioxidant, followed by equol, ascorbic acid, and alpha-tocopherol. Genistein and equol added in combination were more protective than when added singly. Based on these preliminary data, which are similar to those observed previously in lymphocytes, these compounds may have a role to play in antioxidant protection against male infertility.
{"title":"In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm.","authors":"J. Sierens, J. Hartley, M. J. Campbell, A. Leathem, J. Woodside","doi":"10.1002/TCM.10015","DOIUrl":"https://doi.org/10.1002/TCM.10015","url":null,"abstract":"Isoflavones are plant compounds, proposed to have health benefits in a variety of human diseases, including coronary heart disease and endocrine-responsive cancers. Their physiological effects include possible antioxidant activity, therefore suggesting a role for isoflavones in the prevention of male infertility. The aim of this study was to test the antioxidant effects of the isoflavones genistein and equol on sperm DNA integrity, assessed in vitro after hydrogen peroxide-mediated damage, using the comet assay. Pre-treatment with genistein or equol at doses of 0.01-100 micromol/l significantly protected sperm DNA against oxidative damage. Both ascorbic acid (10-600 micromol/l) and alpha-tocopherol (1-100 micromol/l) also protected. Compared with ascorbic acid and alpha-tocopherol, added at physiological concentrations, genistein was the most potent antioxidant, followed by equol, ascorbic acid, and alpha-tocopherol. Genistein and equol added in combination were more protective than when added singly. Based on these preliminary data, which are similar to those observed previously in lymphocytes, these compounds may have a role to play in antioxidant protection against male infertility.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"23 1","pages":"227-34"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77381144","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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