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The alkylating agents ethyl nitrosourea (ENU), isopropyl methanesulphonate (iPMS) and methyl methanesulphonate (MMS) are potent male rodent germ cell mutagens. The mutagenic activity of these compounds in male mouse germ cells has been evaluated using the Muta TM Mouse positive selection transgenic mutation assay. Both ENU (150 mg/kg) and iPMS (100 mg/kg) gave increased mutant frequencies...
Mutant frequencies in male germ cells were determined in mice 3 days after exposure to saline, methylmethane sulfonate (MMS), or ethylnitrosourea (ENU). DNA was isolated from seminiferous tubules by a modified version of the drop dialysis method. A 5-fold increase in mutant frequency was observed in mice treated with ENU. No statistically significant increase was observed in mice treated with MMS.
Recently-developed transgenic models have provided unprecedented access to rodent somatic and germ line tissues for the study of gene mutation in vivo. While mutations in germ cells are considered an important aspect of any regulatory assessment of the risks posed by chemicals, currently-available conventional tests, which involve the study of thousands of offspring make it impractical to test large...
Germ-cell mutagenesis has been studied in male λ lacZ transgenic mice in such a way that the data can be compared with literature data for germ-cell mutagenesis obtained with the specific-locus test (SLT). Mutagenesis induced by ethylnitrosourea (ENU), ethylmethanesulphonate (EMS), methylnitrosourea (MNU) and methylmethanesulphonate (MMS), has been studied in mature spermatozoa isolated from the...
A collaborative study to systematically assess transgenic mouse mutation assays as screens for germ cell mutagens has been conducted. Three male mouse germ cell mutagens (ENU, iPMS and MMS) were selected for testing. This paper provides a brief review of the effects reported for those 3 chemicals in the most commonly used non-transgenic germ cell mutagenicity assays, namely the dominant lethal, heritable...
Three confirmed mouse germ cell mutagens, ethyl nitrosourea (ENU), isopropyl methanesulphonate (iPMS) and methyl methanesulphonate (MMS), have been evaluated for their activity as mutagens to the germ cell DNA of two strains of transgenic mice (lac I, Big Blue TM and LacZ, Muta TM Mouse). Both testicular DNA and epididymal sperm DNA were evaluated. A range of sampling times...
Mutagenesis induced by methyl methanesulfonate (MMS), a germ cell mutagen, in the testis and the sperm isolated from epididymis and vas deferens have been investigated using lacZ transgenic mice (Muta TM Mouse). Male Muta TM Mice were injected intraperitoneally with MMS at a dose of 80 mg/kg, a potent dominant lethal dose. Animals were killed on days 3 and 7 (Experiment...
Male C57Bl/6 lacI transgenic mice were used to evaluate germ cell mutagenesis in vivo as part of a collaborative study. Groups of 10 mice were administered single intraperitoneal doses of ethylnitrosourea (ENU; 150 mg/kg), isopropyl methanesulfonate (IPMS; 200 mg/kg), methyl methanesulfonate (MMS; 40 mg/kg) or vehicle. Epididymal spermatozoa and testes were recovered 3 days later and DNA isolated...
As part of the Germ Cell Collaborative Study, we used the positive-selection Muta TM Mouse model to evaluate the effects of two direct alkylating agents, ethylnitrosourea (ENU) and methyl methanesulfonate (MMS), on male germ cells. The lacZ mutation frequency in seminiferous tubule cells and epididymis spermatozoa was measured 3, 14, 25 and 50 days after a single intraperitoneal (i.p...
The present study was undertaken to clarify whether the transgenic mouse mutagenesis assay system can be used instead of dominant lethals or specific locus test after treatment of male germ cells in mouse with ethylnitrosourea (ENU). Male Big Blue TM transgenic mice (BB) carrying a lacI target gene were given a single intraperitoneal injection of 150 mg/kg ENU. Vasa deferential sperm,...
To assess the correlation between micronucleus induction and human carcinogenicity, the rodent micronucleus assay was performed on known and potential human carcinogens in the 6th MMS/CSGMT collaborative study. Approximately 100 commercially available chemicals and chemical groups on which there was little or no micronucleus assay data were selected from IARC (International Agency for Research on...
Knowledge concerning the genotoxicity of inorganic metal compounds in the SOS chromotest is limited. Up to now, only Cr(VI), Sn(II) and the platinum antitumor compound cisplatin(II) were shown to be genotoxic in this test system. However, for Cr(VI) and Sn(II), a positive reaction could only be achieved in cytotoxic dose ranges. The aim of the present study was to provide additional data concerning...
The bifunctional alkylating agent chlorambucil (CBC) is a chemotherapeutic agent that induces a high yield of mouse germ-line mutations, apparently due to multi-locus deletions or other chromosomal rearrangements. We investigated the mutagenicity of CBC in cultured mammalian cells by comparing its effect in the AS52/gpt and CHO/hprt gene mutation assays, which detect large and small effects, respectively...
The principal natural food colorants used in modern food manufacture are anthocyanins, betalains, carotenoids, chlorophylls, riboflavin and caramel. Carotenoids (carotenes and xanthophylls) occur naturally in some foods such as carrots, red tomatoes, butter, cheese, paprika, palm oil, corn kernels, marigold petals, annatto, and red salmon. Carotenoids (α- or β-carotene and xanthophylls) are excellent...
Platinum and palladium belong to the group of platinum elements and thus share many chemical properties. Platinum coordination complexes are known to be carcinogenic and genotoxic in mammalian and bacterial cells. However, little is known about palladium genotoxicity. This study compares and evaluates the genotoxic potential of selected platinum and palladium metal salts in mammalian and bacterial...
Heritable malformations were examined in the progeny of X-irradiated male medaka (Oryzias latipes) by three-generation crosses. Two X-irradiated male fish were pair-mated with non-irradiated females to produce F 1 founders, and each F 1 fish was pair-mated with a non-irradiated fish to produce F 2 progeny. For detection of recessive mutations, pair-matings between F 2...
The genotoxic effect of dibromoethane is thought to be due to glutathione S-transferase mediated metabolism. The purpose of this study was to determine whether variations in endogenous glutathione in human cells could modify the genotoxicity of dibromoethane. Genotoxicity of dibromoethane, assessed by sister chromatid exchange, was examined in normal human skin fibroblasts and fibroblasts obtained...
A genotoxicity evaluation of three commonly used estrogens - ethinyl estradiol, cyclotriol and cyclodiol was undertaken using short-term in vitro and in vivo assays. None of the drugs caused significantly increased or decreased number of His + mutants to appear in the Ames Salmonella assay, either with or without S9 mix or in a modified host-mediated version of this assay. However, the clastogenic...
The mutagenic potency of nine methylnitrocarbazoles, four methylaminocarbazoles and the methylcarbazole parent compounds was evaluated in Salmonella typhimurium TA98 and TA100, in the absence and presence of S9 isolated from Aroclor-induced rat liver. Nitro derivatives were additionally tested in TA98NR and TA98/1,8DNP 6 , and mutagenicity of nitrocarbazoles bearing methyl groups in positions...
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