RAT AND MOUSE TISSUE-MEDIATED MUTAGENICITY OF RING-SUBSTITUTED 3,3-DIMETHYL-1-PHENYLTRIAZENES IN SALMONELLA-TYPHIMURIUM

Dimethyl-1-phenyltriazene and a series of ring-substituted derivatives (X-.vphi.-N=N-N-(CH3)2: X = substituent(s) .vphi. = phenyl, used as anti-neoplastic agents) were tested for their mutagenic and toxic action upon S. typhimurium G-46 in a liquid incubation system containing 9000 g tissue supernatants and an NADPH-generating system. The compounds could be grouped into 4 classes according to their toxicity and mutagenicity after 1 h incubation at 37.degree. C at a concentration of 5 mM in the presence of liver supernatant fractions from phenobarbitone-pretreated mice. When a liver supernatant from untreated mice was compared with one from phenobarbitone-pretreated animals, the mutagenic effect of a series of triazenes (with X = H: 4-chloro; 4-chloro; 4-bromo; 2,4,6-trichloro) in vitro was enhanced 2-10 times. The toxicity of triazenes with X = 4-methoxy or 4-acetamido was strongly decreased by a liver fraction from phenobarbitone-pretreated mice in the presence of an NADPH-generating system. With 3,3-dimethyl-1-phenyl-triazene, rat liver fractions caused a lower enzyme-mediated mutagenicity in S. typhimurium G-46 than those of mouse liver; a 9000 g supernatant from brain, a major target organ for the carcinogenic action of certain triazenes, was unable, in either species, to generate metabolites mutagenic for S. typhimurium G-46.