Salmonella typhimurium, mutagen induced, inhibition

Genotoxicity studies with A-hydroxyacetamide, a possible metabolite of acetamide, have shown that this agent is weakly mutagenic in Salmonella typhimurium and induces DNA damage in a rat hepatoma cell line. However, it did not bind covalently to DNA in vitro and did not induce morphological transformation of Syrian hamster embryo cells in vitro or inhibit gap-junctional intercellular communication in Chinese hamster lung V79 cells. 

Genotoxic Effects. Genotoxic Effects. HDI was demonstrated to be non-mutagenic against some Salmonella typhimurium strains with or without metabolic activation (Anderson et al. 1980). HDI also inhibited the growth of Ehrlich ascites tumor eells in female mice (Moos et al. 1971) and decreased the mutation frequency in Escherichia coli (Kawazoe et al. 1981). Calf thymus DNA incubated in vitro with 10.4 or 52 mol of HDI for 10 or 20 minutes produeed no evidence of intrastrand cross-links or DNA strand breaks (Peel et al. 1997). No studies were located that studied the genotoxic effects of HDI on human cells or that deseribed the ability of prepolymer forms of HDI to induce genotoxicity."... 

We had previously eliminated the possibility that retinol affected bacterial viability in this assay. The likelihood of a non-specific inhibitory effect of retinol was also eliminated, since there was no effect of vitamin A alcohol on mutagenicity induced by adriamycin, a direct-acting mutagen in Salmonella (23). Thus, these findings demonstrated that retinol inhibited the metabolism of 2-fluorenamine by rat liver tissue preparations to forms capable of producing mutations in S typhimurium. 

Low levels of retinol or retinyl acetate enhance mutagenicity induced by 2-fluorenamine in Salmonella typhimurium when activation is carried out by S9, while inhibiting mutagenicity when activation is mediated by microsomes. 

Sodium fluoride did not induce reverse mutations in Salmonella typhimurium, nor did it induce gene conversion in Saccharomyces cerevisiae. A fluoride level of 0.4-1.0mgl inhibited DNA repair after irradiation of mouse spleen cells in vitro. Sodium fluoride was not mutagenic in cell cultures of human leukocytes at concentrations of 18 and 54mgl . Little or no effect was noted on chromosomes when mouse oocytes were exposed in vitro to a fluoride concentration of 200 mg 1 in media for up to 14 h. 

The assays based on tumor initiation events include the inhibition of DMBA-induced mutagenicity with Salmonella typhimurium strain of bacteria and the induction of quinone reductase in cultivated HeLa cells. The compounds that are inhibitors of DMBA-induced mutagenicity bioassays with Salmonella typhimurium also inhibit preneoplastic lesion formation in mammary organ culture. The induction of quinone-reductase in HeLa cells may indicate cancer chemoprevention activity [29]. 

Sulfur mustard has been found to be genotoxic and mutagenic in several microbial assays. The agent caused alkylation of DNA in the yeast Saccharo-myces cerevisiae (Kircher and Brendel 1983) and interstrand DNA cross-links (Venitt 1968) and inhibition of DNA synthesis (Lawley and Brookes 1965) in Escherichia coli. Using the histidine reversion assay, Stewart et al. (1989a) found that sulfur mustard induced point mutations in Salmonella typhimurium strain TA102 and frameshift mutations in TA 97 but neither type of mutation in strains TA98 and TAIOO. 

---