MUTAGENICITY AND CYP1A INDUCTION BY AZOBENZENES CORRELATES WITH THEIRCARCINOGENICITY

The genotoxicity of six azobenzenes was evaluated in the Ames test, in the presence of an activation system derived from Aroclor 1254-treate d rats. Moreover, the ability of these azobenzenes to induce rat hepat ic CYP1A activities and apoprotein levels, and stimulate their own bio activation to mutagens, was also determined. In the presence of the Ar oclor 1254-activation system, o-aminoazotoluene and 3-methoxy-4-aminoa zobenzene were potent mutagens, whereas 4-aminoazobenzene and 4-diethy laminoazobenzene failed to elicit a positive mutagenic response. A ver y weak mutagenic response was induced by 2-methyl-4-dimethylaminoazobe nzene and by azobenzene. o-aminoazotoluene and 3-methoxy-4-aminoazoben zene were potent inducers of CYP1A activities and apoprotein levels, w hereas the remaining four compounds displayed either very weak or no i nduction capability. None of the azobenzenes studied could induce its own activation to mutagens in the Ames test. All six azobenzenes displ aced [H-3]tetrachlorodibenzo-p-dioxin from the cytosolic Ah receptor, with o-aminoazotoluene and 3-methoxy-4-aminoazobenzene being the most effective. A correlation appears to exist between carcinogenic activit y of azobenzenes in the rat on one hand, and of their mutagenic potent ial and hepatic CYP1 induction on the other. Possible mechanisms accou nting for this relationship are discussed.