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. 1993 Mar 1;90(5):2065–2068. doi: 10.1073/pnas.90.5.2065

Trans-activation of glutathione transferase P gene during chemical hepatocarcinogenesis of the rat.

S Morimura 1, T Suzuki 1, S Hochi 1, A Yuki 1, K Nomura 1, T Kitagawa 1, I Nagatsu 1, M Imagawa 1, M Muramatsu 1
PMCID: PMC46021  PMID: 8446629

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.

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