Trans-activation of glutathione transferase P gene during chemical hepatocarcinogenesis of the rat.
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.
Morimura
S
S
Department of Biochemistry, University of Tokyo Faculty of Medicine, Japan.
Suzuki
T
T
Hochi
S
S
Yuki
A
A
Nomura
K
K
Kitagawa
T
T
Nagatsu
I
I
Imagawa
M
M
Muramatsu
M
M
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
D014408:Biomarkers, Tumor; D005982:Glutathione Transferase