Benz[a]anthracene is a potent liver tumorigen in the neonatal B6C3F(1) mouse

Benz[a]anthracene (BA) has been reported to be a noncarcinogen or a borderl ine weak carcinogen in several chronic bioassay systems. For comparison, we determined its tumorigenicity in the neonatal male B6C3F(1) mouse. Mice we re administered i.p. injections (1600 nmol total dose per mouse) within 24 hrs of birth and at 8 and 15 days of age. BA induced hepatocellular adenoma s and carcinomas in 75 and 25% of the mice, respectively, while the solvent control (DMSO) induced 8 and 4%, respectively. Analysis by RT-PCR indicate d that 86% (12/14) of BA-induced liver tumors had activated ras protooncoge nes, 11 with a pattern of GGC-->CGC at K-ras codon 13. Our results clearly demonstrate that BA is a potent tumorigenicity in the neonatal B6C3F(1) mou se and induces a unique type of K-ras-oncogene activation.