Inhibitory effect of reducing agents on N-acetoxy- and N-hydroxy-2-acetylaminofluorene-induced mutagenesis

The effect of cysteine (alpha-amino-beta-mercaptopropionic acid) on the mutagenic activities of the proximate carcinogen, N-hydroxy-2-acetylaminofluorene, and the ultimate carcinogen, N-acetoxy-2-acetylaminofluorene, was examined by estimating the frequency of his+ revertants of Salmonella typhimurium. Nontoxic concentrations of cysteine significantly reduced the formation of revertants when it was applied concurrently with the two carcinogens. Cysteine showed no detectable effect on mutagenesis when added to bacteria before or after exposure to carcinogens. The magnitude of inhibition of mutagenesis depended on the dose of cysteine and the concentration of the carcinogens. Cysteine at equimolar concentrations inhibited to a larger degree the mutagenesis induced by N-hydroxy-2-acetylaminofluorene than it inhibited that elicited by N-acetoxy-2-acetylaminofluorene. The inhibitory action of cysteamine and glutathione was comparable to that of cysteine. The results appear to be consistent with the assumption that cysteine traps electrophiles prior to their action on DNA.