METABOLIC ACTIVATION OF 2,4-DIAMINOANISOLE, A HAIR-DYE COMPONENT .3. ROLE OF CYTOCHROME-P-450 METABOLISM IN IRREVERSIBLE BINDING INVIVO

Injection of 3H-2,4-diaminoanisole (2,4-DAA) [10-200 mg/kg] into rats led to irreversible binding of liver and kidney proteins. The binding was increased by prior treatment of the animals with phenobarbital and .beta.-naphthoflavone and was decreased after cobalt chloride-pretreatment. Irreversibly bound material was preferentially localized in the microsomal fraction. Pretreatment with diethyl maleate slightly increased liver binding, but was without effect on kidney binding. Non-bound 3H-2,4-DAA was rapidly cleared from plasma, liver and kidneys, whereas considerable irreversibly bound 2,4-DAA could still be demonstrated 24 h after a dose of 100 mg/kg i.p. No irreversible binding to hepatic RNA or DNA could be detected.