REDUCTION OF GLUTATHIONE-S-TRANSFERASE P-FORM MESSENGER-RNA EXPRESSION IN REMODELING NODULES IN RAT-LIVER REVEALED BY IN-SITU HYBRIDIZATION

Glutathione S-transferase P-form (GST-P) mRNA levels and distribution were sequentially analyzed by in situ hybridization histochemistry (IS H) in rat livers during and after induction of preneoplastic foci and nodules in the Solt-Farber model, Dot blot analysis showed GST-P trans cripts in the liver to be elevated coincidental with the development o f GST-P-positive lesions, GST-P ISH indicated that the majority of ear ly foci and some of the resultant lesions showed uniformly high levels of GST-P mRNA, However, the majority of foci and nodules after comple tion of the selection regimen exhibited a progressive loss of staining for GST-P mRNA, Similar results were obtained for gamma-glutamyltrans ferase (GGT) transcripts, indicating that phenotypic reversion is cont rolled by factors operating at the level of gene expression in both ca ses, Expression of GST-P mRNA was high in all hepatocellular carcinoma samples, whereas the levels of GGT transcripts varied considerably, s o that the two enzymes showed a degree of independence in their regula tion, The present data for transcription suggest that GST-P is a stabl e marker of preneoplastic and neoplastic cells, not only at the protei n but also at the mRNA level, throughout hepatocarcinogenesis in the r at. The reason why transcription of GST-P mRNA is switched off as part of the reversion to a normal organization remains to be elucidated.