M. Degawa, M. Nakayama, Katsuyuki Fukuda
1995
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Quality indicators
Journal
Drug Metabolism and Pharmacokinetics
Abstract
Male F344 rats were treated with a chemical (aniline, nitrobenzene, 2-methoxy-p-phenylenediamine, 2-methoxy-4-nitroaniline or 2-methoxy-4-nitroazobenzene) produced by the azo-reduction and/or N-oxidation of 2-methoxy-4-aminoazobenzene, a selective inducer of CYP1A2, and effects of their chemicals on CYP1A induction in the liver were examined at the levels of mRNA, protein and enzyme activity. 2-Methoxy-4-nitroaniline and 2-methoxy-4-nitroazobenzene, but not other chemicals used, induced CYP1A enzymes, mainly CYP1A2, as assessed by Western and Northern blots. It is noteworthy that 2-methoxy-4-nitroaniline was more selective than 2-methoxy-4-aminoazobenzene for induction of CYP1A2, and it has the smallest molecular size among known CYP1A2 inducers. Although in induction of CYP1A1 by a polycyclic aryl hydrocarbon (Ah) is thought to be regulated though Ah receptor, cellular component(s) other than Ah receptor would play an important role in the induction of CYP1A2. Presence of a structural unit such as “bay-region” in benzo[a]pyrene molecule or “polyhalogenated aromatic ring” in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin molecule is reportedly requisite for binding of the chemical to Ah receptor, but such structural unit is absent in 2-methoxy-4-nitroaniline molecule.