title: Trans-activation of glutathione transferase P gene during chemical hepatocarcinogenesis of the rat.
abstract: Glutathione transferase P (GST-P; glutathione transferase, EC 2.5.1.18) is known to be specifically expressed at high levels in precancerous lesions and in hepatocellular carcinomas from a very early phase of chemically induced hepatocarcinogenesis in the rat. The almost invariable occurrence of this phenotype in these lesions strongly suggests a mechanism by which GST-P gene is activated together with a crucial transforming gene of liver cells. To distinguish the two alternative possibilities--either the GST-P gene is coactivated with a closely located transforming gene by a cis mechanism or it is activated in trans by a common trans-acting factor--we carried out carcinogenesis experiments using transgenic rats harboring the bacterial chloramphenicol acetyltransferase reporter gene ligated to the upstream regulatory sequence of the GST-P gene. In each of three independent lines tested, liver foci and nodules produced by chemical carcinogens (Solt-Farber procedure) were found to express high levels of chloramphenicol acetyltransferase activity, indicating clearly that the GST-P gene is activated by a trans mechanism during hepatocarcinogenesis.
authors.affiliation: Department of Biochemistry, University of Tokyo Faculty of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Morimura
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Hochi
authors.forename: A
authors.initials: A
authors.lastname: Yuki
authors.forename: K
authors.initials: K
authors.lastname: Nomura
authors.forename: T
authors.initials: T
authors.lastname: Kitagawa
authors.forename: I
authors.initials: I
authors.lastname: Nagatsu
authors.forename: M
authors.initials: M
authors.lastname: Imagawa
authors.forename: M
authors.initials: M
authors.lastname: Muramatsu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D014408:Biomarkers, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics*; D011230:Precancerous Conditions / Q000201:enzymology; D051381:Rats; D015533:Transcriptional Activation
chemical_list: D014408:Biomarkers, Tumor; D005982:Glutathione Transferase