UDP glucuronosyltransferase gene expression is involved in the stimulation of ascorbic acid biosynthesis by xenobiotics in rats.
Wistar-Shi (genotype +/+), heterozygous Gunn (j/+) and homozygous Gunn (j/j) rats was 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.
Horio
F
F
Department of Agricultural Chemistry, School of Agricultural Sciences, Nagoya University, Japan.
Shibata
T
T
Makino
S
S
Machino
S
S
Hayashi
Y
Y
Hattori
T
T
Yoshida
A
A
D000704:Analysis of Variance; D000818:Animals; D001205:Ascorbic Acid / Q000096:biosynthesis* / Q000652:urine; D001483:Base Sequence; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D002701:Chloramphenicol / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D007274:Injections, Intraperitoneal; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D008748:Methylcholanthrene / Q000008:administration & dosage / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D011911:Rats, Gunn; D011919:Rats, Inbred Strains; D013997:Time Factors; D015262:Xenobiotics / Q000494:pharmacology*
D009596:Nitrophenols; D012333:RNA, Messenger; D015262:Xenobiotics; D008748:Methylcholanthrene; D002701:Chloramphenicol; D014453:Glucuronosyltransferase; D001205:Ascorbic Acid; C024836:4-nitrophenol; D010634:Phenobarbital