Induction of a high spin form of microsomal cytochrome P-448 in rat liver by 4-aminoazobenzene derivatives

Biochemical Pharmacology
M DegawaY Hashimoto

Abstract

Male Sprague-Dawley rats were treated with 4-aminoazobenzene derivatives or other drug metabolizing enzyme inducers such as phenobarbital, 3-methylcholanthrene and isosafrole. The expression of hepatic microsomal cytochrome P-450 of the rats, principally that of a high spin form of cytochrome P-448 (cytochrome P-448H), was assessed by a bacterial mutation test and by immunological methods. The results of the mutation test with use of Salmonella typhimurium TA9 and 3 aromatic amine substrates showed that 2-methoxyl, 3-methoxyl and 2',3-dimethoxyl derivatives of AAB and methyl derivatives of AAB such as o-aminoazotoluene, N-methyl-4-aminoazobenzene and N,N-dimethyl-4-aminoazobenzene have a large capacity for the selective induction of cytochrome P-448H. Activity of the cytochrome increased by 6 hr after an azo dye treatment, reached a maximum after 24 hr, and then declined. In contrast, 4'-methoxy-AAB has a small, and AAB has no, capacity for the cytochrome induction. The aminoazo dye-induced enzymes differ in their substrate specificities from those induced with 3-methylcholanthrene or phenobarbital, and the induced enzyme was identified to be cytochrome P-448H, as determined by an enzyme-linked immunosorbent assay and immunoblo...Continue Reading

Citations

Feb 1, 1989·Japanese Journal of Cancer Research : Gann·M NamikiY Hashimoto
Nov 13, 1987·Biochemical and Biophysical Research Communications·T HishinumaY Hashimoto
Jun 1, 1995·Japanese Journal of Cancer Research : Gann·M DegawaY Hashimoto
Aug 1, 1997·Human & Experimental Toxicology·P HlavicaJ Schulze

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