Enhancing Effect of a Choline–deficient Diet on Alterations of Hepatic Drug–metabolizing Enzymes in Hepatitis– and Hepatoma–predisposed Rats (LEC Rats)

Marked alterations of hepatic drug–metabolizing enzymes were observed in hepatitis– and hepatoma–predisposed rats (LEC rats) fed a choline–deficient diet. The diet enhanced the development of hepatitis with severe jaundice. The levels of two major classes of cytochrome P–450, P–450(PB) and P–450(MC), were markedly decreased. GST–Yp was dramatically increased, whereas GST–Ya, Ybl and Yb2 were decreased. LEA rats (the control rats to LEC) fed a choline–deficient diet mimicked LEC rats fed a normal diet in terms of the above enzyme alterations, indicating that hypomethylation is involved in the pathogenesis of hepatitis and hepatoma in LEC rats. Such hypomethylation may initiate the hepatocytes that spontaneously develop hepatitis and hepatoma.