ENHANCED HEPATOCARCINOGENESIS IN ACATALASEMIC MICE TREATED WITH DIETHYLNITROSAMINE

Diethylnitrosamine (DEN)-induced hepatocellular carcinogenesis was com pared between C3H/AnLC(s)(b)C(s)(b) (acatalasemic) and C3H/AnLC(s)(a)C (s)(a) (normal) mice. A total of 31 normal and 38 acatalasemic male mi ce, average age 9 weeks, received a single intraperitoneal injection o f DEN (75 mg/kg body wt) weekly for 6 weeks. All animals that survived until the end of week 31 (25th week after the last injection of DEN) were sacrificed and the development of liver tumors was found. They gr ossly varied from one to multiple in number and from 1 to 15 mm in dia meter in both groups. The numbers and size of liver tumors per liver w ere significantly greater (P < 0.05) in acatalasemic mice (mean +/- S. D.: 3.8 +/- 2.0 in number per liver; 9.6 +/- 7.4 in mm diameter per li ver) than in normal mice (1.8 +/- 1.1 in number per liver; 2.8 +/- 1.9 in mm diameter per liver). Histological examination of the tumor tiss ues revealed the development of well-differentiated hepatocellular car cinomas. We suggest that H2O2 or (OH)-O-. formed from H2O2 is likely t o be involved in DEN-induced hepatocarcinogenesis and catalase plays a critical role in the prevention of hepatocarcinogenesis. (C) 1998 Els evier Science Ireland Ltd. All rights reserved.