Induction of drug metabolism-related enzymes by methylcholanthrene and phenobarbital in transgenic mice carrying human prototype c-Ha-ras gene and their wild type littermates
Y. Ohnishi et al., Induction of drug metabolism-related enzymes by methylcholanthrene and phenobarbital in transgenic mice carrying human prototype c-Ha-ras gene and their wild type littermates, EXP ANIM, 50(1), 2001, pp. 33-39
Transgenic mice hemizygously carrying human c-Ha-ras proto-oncogene, Tg-ras
H2 show Very sensitive and facilitated carcinogenicity to various carcinoge
ns. In this study, activities of certain enzymes related to drug metabolism
and energy metabolism were measured in microsome and cytosol fractions of
livers of Tg-rasH2 mice and their wild type littermates with both sexes tre
ated with 3-methylcholanthrene (MC) and phenobarbital (PB). Aminopyrine N-d
emethylase activities increased significantly in livers of all mice treated
with PB. MC and PB treatments induced significant increases in activities
of UDP-glucuronosyltransferase and S-adenosyl homocysteinase compared to th
ose in the non-treated groups in microsome fractions from all mice. In cyto
sol fractions of livers of all mice, glutathione S-transferase activity was
significantly induced in the PB treated groups. There were no significant
differences in activities of lactate dehydrogenase, glucose g-phosphate deh
ydrogenase, pyruvate kinase and glucose 6-phosphatase related to energy met
abolism in livers and kidneys among all mice. Tg-rasH2 mice showed stable a
ctivities of enzymes related to drug detoxication and energy metabolism sim
ilar to those of non-transgenic mice. These results suggest that the human
c-Ha-ras transgene may not affect drug metabolism-related enzymes, and the
facilitated carcinogenic response in the Tg-rasH2 mouse is not due to these
enzymatic disorders.