title: Cell type-specific induction of O6-alkylguanine-DNA alkyltransferase mRNA expression in rat liver during regeneration, inflammation and preneoplasia.
abstract: OBJECTIVE
  To investigate the potential role of an aberrant cellular DNA repair in target cells during malignant transformation we studied cell type-specific mRNA expression of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (O6-AGT) in normal and regenerating rat liver, chronic hepatitis and preneoplastic liver lesions by in situ hybridization and semiautomatic image analysis.
  
  
  RESULTS
  O6-AGT mRNA expression was found to be four to five times higher in hepatocytes than in nonparenchymal cells. A 1.9-fold increase in O6-AGT mRNA was observed after partial hepatectomy. Intraperitoneal injection of diethylnitrosamine led to a 1.3-fold and 2.6-fold rise in periportal and perivenous hepatocytes, respectively. Ethylnitrosourea produced an enhancement of mRNA levels up to 1.6-fold in hepatocytes without regional differences. In megalocytic hepatocytes of Long-Evans Cinnamon rats with chronic hepatitis, a 4.4-fold mRNA induction was found. In small preneoplastic lesions induced after chronic diethylnitrosamine-exposure, O6-AGT mRNA expression was identical to that of adjacent normal tissue. Intermediate and large lesions revealed 1.5- to 1.6-fold higher mRNA levels.
  
  
  CONCLUSIONS
  These results suggest an induction of O6-AGT mRNA expression in hepatocellular target tissue under conditions of increased carcinogen sensitivity . The O6-AGT expression in early preneoplastic lesions did not differ from normal surrounding liver tissue, thus excluding the possibility that progression of preneoplasia in rat liver is associated with a deficient mRNA expression of this DNA repair protein. On the contrary, enhanced O6-AGT mRNA expression in more advanced foci and early neoplastic nodules may confer a selective advantage upon early malignant hepatocytes with regard to further tumor progression.
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University Munich, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Vielhauer
authors.forename: M
authors.initials: M
authors.lastname: Sarafoff
authors.forename: P
authors.initials: P
authors.lastname: Gais
authors.forename: H M
authors.initials: HM
authors.lastname: Rabes
mesh_terms: D000818:Animals; D004128:Dimethylnitrosamine; D004790:Enzyme Induction; D017403:In Situ Hybridization; D007249:Inflammation / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D008115:Liver Regeneration; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011230:Precancerous Conditions / Q000201:enzymology*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D014158:Transcription, Genetic
chemical_list: D019853:O(6)-Methylguanine-DNA Methyltransferase; D004128:Dimethylnitrosamine