Induction of hepatic microsomal cytochrome P-448 by 3,3',4,4'-tetrachloroazobenzene and the corresponding azoxy and hydrazo analogs.

3,3',4,4'-Tetrachlorazobenzene (TCAB) has been found to pose occupational health hazards among chemical workers as a consequence of its contamination in commercially important herbicides. The induction of hepatic microsomal cytochrome levels in male rats treated with TCAB or its azoxy and hydrazo analogs were examined in several short-term experiments. Five daily consecutive administrations of TCAB or 3,3',4,4'-tetrachloroazoxybenzene (TCAOB) at doses of 25 mg/kg/day yielded maximal stimulation of cytochrome levels. Both compounds induced cytochrome P-450 with absorption maxima (reduced, CO complex) at 448 nm to 2.7 times control levels. In contrast, cytochrome P-448 levels were enhanced less than twofold relative to controls in animals treated with 3,3',4,4'-tetarchlorohydrazobenzene (TCHB) under identical conditions. Cytochrome inductions arising from these chemicals are dose dependent. Parallel increase of the liver to body weight ratios was also observed in these studies. Further experiments using different regimens indicated TCAOB as being the most potent and persistent inducer among these three analogs. A twofold enhancement of cytochome P-448 levels was observed 14 days after a single ip injection of TCAOB at doses as low as 10 mg/kg.