Enhanced hepatocarcinogenesis in acatalasemic mice treated with diethylnitrosamine

Diethylnitrosamine (DEN)-induced hepatocellular carcinogenesis was compared 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 mice, average age 9 weeks, received a single intraperitoneal injection of 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 grossly varied from one to multiple in number and from i to 15 mm in diameter in both groups. The numbers and size of liver tumors per liver were 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 liver) 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 tissues revealed the development of well-differentiated hepatocellular carcinomas. We suggest that H₂O₂ or ·OH formed from H₂O₂ is likely to be involved in DEN-induced hepatocarcinogenesis and catalase plays a critical role in the prevention of hepatocarcinogenesis.