Rat and mouse tissue-mediated mutagenicity of ring-substituted 3,3-dimethyl-1-phenyltriazenes in Salmonella typhimurium

Abstract

3,3-Dimethyl-1-phenyltriazene and a series of ring-substituted derivatives X4ØN=N( CH 3) 3: X = substituent(s); ø = phenyl) were tested for their mutagenic and toxic action upon Salmonella typhimurium G-46 in a liquid incubation system containing 9000 g tissue supernatants and an NADPH-generating system. The compounds could be grouped into four classes according to their toxicity and mutagenicity after 1 h incubation at 37°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 twice to ten 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,, whereas 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.