Progression of Tumor Histiotype during Mouse Hepatocarcinogenesis Associated with the Viable Yellow (Avy)Gene1

Increasing attention has been focused recently upon those factors in carcinogenesis that are responsible for the proliferation of initiated cells and the increasingly aberrant phenotype that they progressively manifest. The agouti locus alÃ-ele/(" (viable yellow) has been shown to be associated with conditions which favor promotion of cells that have been initiated by a wide variety of causes, in many organs, but has not been previously associated with tumor progression in those systems. In the current study, the presence of the A'y gene in a strain of mice not normally predisposed to hepatocarcinogenesis, C57BL/6N was, for the first time, associated not only with much earlier appearance, but with progression of the histiotype of hepatic tumors, following neonatal administration of diet hylnitrosamine. At 52 weeks, 28 C57BL/6N mice demonstrated 7 mouse liver tumors 0.5 cm or greater in diameter, all of more benign histiotype, without associated metastasis. The 31 i '57BL/6N-/T1' demonstrated 194 mouse liver tumors at that time, 22% of which were of malignant histiotype, 19% of which were associated with metastasis. This system would appear to offer the possibility of identifying the underlying mech anisms for components of the carcinogenic process. In addition, the ( '57BI,/6\!-.-(r'' mouse appears to offer advantages as a test animal in bioassay procedures that use the liver as a target organ. Thus, it represents a mouse with little or no spontaneous predisposition to hepatocarcinogenesis, with a predicted short lag period toward re sponse to hepatocarcinogens.