Mutagenicity and CYP1A induction by azobenzenes correlates with their carcinogenicity

The genotoxicity of six azobenzenes was evaluated in the Amestest, in the presence of an activation system derived from Aroclor1254-treated rats. Moreover, the ability of these azobenzenesto induce rat hepatic CYP1A activities and apoprotein levels,and stimulate their own bioactivation to mutagens, was alsodetermined. In the presence of the Arodor 1254-activation system,o-aminoazotoluene and 3-methoxy-4-aminoazobenzene were potentmutagens, whereas 4-amino- azobenzene and 4-dlethylaininoazobenzenefailed to elicit a positive mutagenic response. A very weakmutagenic response was induced by 2-methyl-4-dimethylaininoazobenzeneand by azobenzene. o-Aminoazotoluene and 3-methoxy-4-amino-azobenzene were potent inducers of CYP1A activities and apoproteinlevels, whereas the remaining four compounds displayed eithervery weak or no induction capability. None of the azobenzenesstudied could induce its own activation to mutagens in the Amestest. All six azobenzenes displaced [ from the cytosolic Ahreceptor, with o-amlnoazotoluene and 3-methoxy-4-aminoazo- benzenebeing the most effective. A correlation appears to exist betweencarcinogenic activity of azobenzenes in the rat on one hand,and of their mutagenic potential and hepatic CYP1 inductionon the other. Possible mechanisms accounting for this relationshipare discussed.