UDP glucuronosyltransferase gene expression is involved in the stimulation of ascorbic acid biosynthesis by xenobiotics in rats
1993
Horio, F. | Shibata, T. | Makino, S. | Machino, S. | Hayashi, Y. | Hattori, T. | Yoshida, A.
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.
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