Relative mutagenic and prophage-inducing effects of mono- and di-alkyl nitrosoureas.
Mutagenic capacity, prophage-inducing ability, and decomposition rates of mono- and di-alkylnitrosoureas with the same alkyl groups were studied in aqueous systems using S. typhimurium strain TA1535 and E. coli strain BR339 (lambda). Slower decomposition rates of nitrosodialkylureas compared with monoalkylnitrosoureas were not reflected in reduced mutagenicity, with the exception of the methylating agents. With the monoalkylnitrosoureas, mutagenicity varied with length of the alkyl chain, and was greatly increased by oxygen substituents. Among the dialkylnitrosoureas, mutagenesis and decomposition rates were dependent on the substitutent in the N-1 position, adjacent to the nitroso group. Prophage induction, on the other hand, was dependent on a substituent in the N-3 position. The results suggested the existence of two distinct mechanisms for DNA damage, one SOS-dependent and the other SOS-independent, by which different dialkylnitrosoureas acted. Neither in vitro assay system was a reasonable model for the carcinogenic activity of these compounds.
D000478:Alkylation; D010582:Bacteriophage lambda / Q000187:drug effects; D004249:DNA Damage; D004269:DNA, Bacterial / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects; D009152:Mutagenicity Tests; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014775:Virus Activation / Q000187:drug effects*
D004269:DNA, Bacterial; D004279:DNA, Viral; D009607:Nitrosourea Compounds