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

Citation
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
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Animal Sciences
Journal title
EXPERIMENTAL ANIMALS
ISSN journal
1341-1357 → ACNP
Volume
50
Issue
1
Year of publication
2001
Pages
33 - 39
Database
ISI
SICI code
1341-1357(200101)50:1<33:IODMEB>2.0.ZU;2-N
Abstract
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.