TL;DR: To investigate the pattern of inter-specific sensitivity to micronucleus induction three species of fish were exposed to the clastogens bleomycin, cyclophosphamide (CP), 5-fluorouracil (5-FU), and mitomycin C (MMC), and T. rendalii was the most sensitive species to clastogen.
Abstract: Fish are often used for screening genotoxicity of water. For such programs, a knowledge of the sensitivity to clastogens, spontaneous micronucleus frequency and cell cycle kinetics of the target tissue is necessary. To investigate the pattern of inter-specific sensitivity to micronucleus induction three species of fish, Tilapia rendalli, Oreochromis niloticus and Cyprinus carpio, were exposed to the clastogens bleomycin (BLM), cyclophosphamide (CP), 5-fluorouracil (5-FU), and mitomycin C (MMC). The binucleate/mononucleate ratio in peripheral erythrocytes exposed to cytochalasin B was also used to evaluate the time-dependent response of micronucleus formation during hematopoesis in the kidney and the micronucleus peak in peripheral erythrocytes. Micronucleus frequencies induced by CP were significantly greater than their respective controls for the three fish species throughout all treatment periods. During the whole evaluation period (30 days) CP was also the most effective clastogen. In general, until the 14th day of evaluation period T. rendalii was the most sensitive species to clastogens. No difference in micronucleus frequencies among species was observed in the 4th evaluation (at the 30th day). A micronucleus peak was observed at the 7th day after treatment. After the 14th day the frequencies were stabilized. The cytochalasin B experiment was carried out to demonstrate that micronuclei induced in the young kidney erythrocyte cells were detected in the circulating blood 2-4 days later.
TL;DR: It is concluded that clastogenesis occurs primarily at highly cytotoxic arsenic concentrations, casting further doubt as to whether a genotoxic mode of action (MOA) for arsenicals is supportable.
TL;DR: A model micronucleus test system using peripheral blood erythrocytes from larvae of Pleurodeles waltl, which can be used as a monitoring system for the detection of fresh water pollution and for clastogen screening of chemical compounds.
Abstract: A model micronucleus test system using peripheral blood erythrocytes from larvae of Pleurodeles waltl is described. The most suitable larval stage for testing chemical treatments was determined. Larvae were reared in water containing one of the 4 compounds: benzo[a]pyrene (BaP), ethyl methanesulphonate (EMS), diethyl sulphate (DES) and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Response curves as a function of treatment duration over a period of 16 days were plotted for 3 different concentrations of the 4 compounds in order to optimize conditions for a low dose micronucleus test. This model can be used as a monitoring system for the detection of fresh water pollution and can also be employed for clastogen screening of chemical compounds. The test is sensitive, reliable and easy to use.
TL;DR: The weight of evidence supports the conclusion that arsenic is either inactive or extremely weak for the induction of gene mutations in vitro and that arsenic may affect DNA by the inhibition of DNA repair processes or by its occasional substitution for phosphorus in the DNA backbone.
Abstract: Various inorganic compounds of arsenic have been tested for mutagenicity in a variety of test systems ranging in complexity from bacteria to peripheral lymphocytes of exposed human beings. Although much of the data are contradictory, the weight of evidence supports the following conclusions: 1) arsenic is either inactive or extremely weak for the induction of gene mutations in vitro; 2) arsenic is clastogenic and induces sister chromatid exchanges (SCE) in a variety of cell types, including human cells, in vitro; trivalent arsenic is approximately an order of magnitude more potent than pentavalent arsenic; 3) arsenic does not appear to induce chromosome aberrations in vivo in experimental animals; 4) several studies suggest that human beings exposed to arsenic demonstrate higher frequencies of SCE and chromosomal aberrations in peripheral lymphocytes; 5) arsenic may affect DNA by the inhibition of DNA repair processes or by its occasional substitution for phosphorus in the DNA backbone. A summary of this literature is included in this article.
TL;DR: In the National Toxicology Program database of 172 chemicals that was judged non-carcinogenic or equivocal in 2 year rodent studies in both sexes of rats and mice, there are 38 chemicals that were mutagenic in Salmonella.
Abstract: In the National Toxicology Program database of 172 chemicals that were judged non-carcinogenic or equivocal in 2 year rodent studies in both sexes of rats and mice, there are 38 chemicals that were mutagenic in Salmonella. All but two of the chemicals had structural alerts for mutagenicity. The largest proportion of the mutagenic non-carcinogens were benzeneamines and substituted benzeneamines. In all, 12 of the mutagenic non-carcinogens had mutagenic carcinogen analogues, and for two chemicals, the carcinogenic analogues were not mutagenic. Non-carcinogens that were mutagenic in Salmonella also tended to be mutagenic and clastogenic in mammalian in vitro tests. The mutagenic responses are discussed and explanations offered for the mutagenicity and lack of carcinogenic activity of these chemicals.