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Sex Differences in Biotransformation of the Xenobiotic p-Nitroanisole in Isolated Rat Hepatocytes under the Influence of Phenobarbital

S. P. Mazur1 and A. Yu. Petrenko1,2

1Institute for Problems of Cryobiology and Cryomedicine, National Academy of Science of Ukraine, ul. Pereyaslavskaya 23, Kharkov, 310015 Ukraine; fax: (0572) 71-00-84; E-mail: pay@pay.kharkov.ua

2To whom correspondence should be addressed.

Submitted may 23, 1996; revision submitted January 11, 1997.

Different sensitivity of the xenobiotic biotransformation system to phenobarbital treatment in female and male rat hepatocytes is shown. Hepatocytes isolated from females had less cytochrome P-450 content and metabolized the xenobiotic p-nitroanisole (p-NA) more slowly than hepatocytes from males. Phenobarbital treatment increased the cytochrome P-450 amount and the p-nitrophenol (p-NPh) formation rate in hepatocytes from female and male rats to the same extent. However, in control and female induced cells the main form of p-NPh was as conjugates, while induction of male rats reactions of conjugation were depressed and free p-NPh accumulated. The sex differences in the response of xenobiotic biotransformation system to an inducing treatment should be taken into account in transplantation and prescription of drug treatment courses.

KEY WORDS: hepatocyte, xenobiotic metabolism, p-nitroanisole, phenobarbital, sex.