Abstract
The administration of xenobiotics, such as 3-methylcholanthrene (MC), phenobarbital (PB), polychlorinated biphenyls (PCB) and aminopyrine, iduces biosynthesis of ascorbic acid (AsA) in rats, resulting in the increase in urinary excretion of AsA and the accumulation of AsA in various tissues. It is speculated that requirement of AsA in animals unable to synthesize AsA is increased by feeding xenobiotics. AsA is synthesized from D-glucose in liver in rats. We here show the regulatory mechanism on the stimulation of AsA biosynthesis by xenobiotics in rats. We previously demonstrated that hepatic activity of UDP glucuronosyltransferase (UDPGT) is induced more than 10-fold by the administration of xenobiotics. In this study, two strains of rat mutant, such as Gunn rat and EHBR (Eisai hyperbilirubinuria rat), were used for elucidating the role of UDPGT and β-glucuronidase in AsA biosynthesis. Gunn rat has a hereditary defect in MC-inducible UDPGT. The administration of MC did not stimulate AsA biosynthesis in the Gunn rats, but the administration of PB markedly induced AsA biosynthesis in this mutant. EHBR has an extremely low activity of microsomal β-glucuronidase in liver. The stimulation of AsA biosynthesis by MC or PB was markedly suppressed in EHBR compared with that in normal rats. The data indicate that the stimulation of the expression of UDPGT genes play a key role in the AsA biosynthesis induced by xenobiotics, such as MC and PB.
