[Influence of compensatory hepatocyte proliferation on the carcinogenesis of N-nitrosodimethylamine].

OBJECTIVE

To study the influence of compensatory hepatocyte proliferation on the N-nitrosodimethylamine (NDMA) carcinogenesis in rats.

METHODS

NDMA was given to animals of the experimental group 24 hours after partial hepatectomy, and the control group was only treated with NDMA. Expression of gamma-glutamyltransferase (GGT), glutathione S-transferase placental form (GSTP), proliferating cell nuclear antigen (PCNA), insulin-like growth factor-II (IGF-II) and oncogenes was detected.

RESULTS

The numbers and areas of GGT- and GSTP-foci in the experimental group were significantly increased in comparing with the control groups. The expression of GSTP was higher than that of GGT. The total tumor incidence of the experimental group was higher than that of the control by the end of the 56th week. Up to week 71, the incidences of liver and other tumors were higher respectively in the experimental group. The amount of PCNA positive cells were corresponding with proliferative condition of the hepatic lesions. The expression of IGF-II, c-myc and H-ras mRNA increased in the altered hepatocyte foci and nodules, but markedly decreased in hepatocellular carcinoma and adenoma. No c-jun mRNA expression was detected in all the normal and abnormal tissues of liver.

CONCLUSIONS

The results suggest that compensatory hepatocyte proliferation enhances the carcinogenesis induced by multiple doses of NDMA, and the over expression of IGF-II, c-myc, H-ras may play a synergetic role in NDMA-induced hepatocarcinogenesis.