Diethylnitrosamine-induced hepatocarcinogenesis in recombinant inbred mouse strains: Correlation with serum levels of alpha-fetoprotein

Males from seven strains of Recombinant Inbred mice (RIs) were exposed to a single intraperitoneal (IP) dose of Diethylnitrosamine (DEN) 10 mg/kg on day 15 of age. After weaning, mice were maintained on normal lab chow, and euthanized at 40 weeks of age. 97% of the mice developed liver tumors and 98% of mice demonstrated elevated levels of serum Alpha-fetoprotein (AFP). Serum AFP levels were higher in mice bearing hepatomas than in mice bearing only adenomas. The preceding report described the spontaneous occurrence of liver tumors in these seven RI strains at 24 months of age. Although many more tumors occurred in mouse strains induced by DEN carcinogenesis than occurred spontaneously in the same RIs, significant differences were found between strains in both studies. The single dose of DEN initiated multiple adenomas in most mice, some of which progressed to carcinomas by 40 weeks. We conclude that serum AFP levels are a useful predictor of liver tumors during DEN carcinogenesis in these 7 RI strains.