Inhibitory effects of thiols on a mutagenic contaminant from the synthesis of N-nitrosothiazolidine.
The effect of S9 and various thiols were studied for potential modifying effects on a mutagenic trace artifact ('NTHZ') formed during the synthesis of N-nitrosothiazolidine (NTHZ) from cysteamine, formaldehyde and nitrite. Induced and uninduced S9 prepared from Syrian hamster livers reduced mutagenic activity in Salmonella TA100. Incorporation of boiled S9 into the preincubation medium produced similar effects, indicating a non-enzymatic mechanism for the detoxification reaction. Thiols alone also lowered revertant yields, and inhibitory efficacy was, in general, related to the pKa of the compound. At equimolar concentrations mutagenic activity was reduced in the following order (pKa values in parentheses): Thioglycolate (10.7) greater than mercaptoethanol (9.6) greater than reduced glutathione (8.8) greater than cysteine (8.35) greater than cystine (8.2). N-Acetylcysteine (9.52) and cysteamine (8.35), however, did not fit this pattern. The results of this study suggest that normal hepatic mechanisms may minimize 'NTHZ' genotoxicity thereby reducing potential health risks associated with its exposure.
Miller
A J
AJ
Fiddler
W
W
D000818:Animals; D006224:Cricetinae; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens / Q000037:antagonists & inhibitors*; D009603:Nitroso Compounds / Q000138:chemical synthesis / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis / Q000633:toxicity*
D009153:Mutagens; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D013844:Thiazoles; C042199:N-nitrosothiazolidine