Liver lesions in B6C3F1 mice: the National Toxicology Program, experience and position

The spectrum of hepatocellular proliferative lesions in B6C3F1 (C57BL/6N X C3H/HeN MTV-) mice used in National Toxicology Program (NTP) two-year carcinogenicity studies includes foci of cellular alteration, adenoma, carcinoma, and hepatoblastoma. The diagnosis of hepatocellular hyperplasia is reserved for those non-neoplastic proliferative lesions which are believed to occur secondary to necrosis or a degenerative process in the liver. Diagnostic criteria, similar to those previously published, are used during the NTP peer review of these lesions. Incidences of liver tumors in control mice have been established from the NTP database and the frequency of enhanced liver tumor responses in treated mice has been determined based on 278 two-year carcinogenicity studies. Although alternative rodent strains are being examined, at the present time there is no acceptable alternative to the B6C3F1 mouse for NTP carcinogenicity studies. Interim sacrifices and "stop" studies are incorporated into two-year studies to gain knowledge about the biological behavior of mouse liver neoplasia. Also, data are being gathered relative to the pattern of oncogene activation in spontaneous and chemically induced liver tumors in B6C3F1 mice.