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UDP Glucuronosyltransferase Gene Expression is Involved in the Stimulation of Ascorbic Acid Biosynthesis by Xenobiotics in Rats^1,2,

Department of Agricultural Chemistry, School of Agricultural Sciences, Nagoya University, Nagoya 464-01, Japan ^* Aburahi Laboratories, Shionogi & Co., Ltd., Shiga 520-34, Japan ^** Center for Molecular Biology and Genetics, Mie University, Tsu 514, Japan

Wistar-Shi (genotype +/+), heterozygous Gunn (j/+) and homozygous Gunn (j/j) rats were injected intraperitoneally with 3-methylcholanthrene (3MC) dissolved in corn oil. In rats of all genotypes the hepatic concentration of UDP glucuronosyltransferase (UDPGT) mRNA was increased at 48 and 96 h after the treatment with 3MC. Hepatic activity of 4-nitrophenol UDPGT was increased by 3MC in Wistar-Shi rats and heterozygous Gunn rats but not in homozygous Gunn rats. Urinary ascorbic acid excretion increased 72 and 96 h after the injection with 3MC in Wistar-Shi and heterozygous Gunn rats but not in homozygous Gunn rats. Ninety-six hours after the injection with 3MC, the hepatic concentration of ascorbic acid in Wistar-Shi rats was 90% higher than that in the corresponding control group, whereas in heterozygous and homozygous Gunn rats the increases were 70 and 30%, respectively. Wistar-Shi rats and homozygous Gunn rats were also injected daily for 3 d with sodium phenobarbital. In rats of both genotypes, the activity and hepatic concentration of chloramphenicol-UDPGT mRNA and liver and urine ascorbic acid concentration were increased by sodium phenobarbital. The data indicate that the stimulation of the expression of both the 4-nitrophenol and chloramphenicol UDPGT genes plays a key role in the ascorbic acid biosynthesis induced by 3MC and sodium phenobarbital.

KEY WORDS: • UDP glucuronosyltransferase mRNA • rats • ascorbic acid • xenobiotics

¹ Supported in part by a grant of the Elizabeth Arnold Fuji Foundation.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence and reprint requests should be addressed.

Manuscript received 1 March 1993. Initial review completed 1 June 1993. Revision accepted 22 July 1993.

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