Use of rodent hepatocytes for metabolic activation in transformation assays

Although the evidence is not definitive, available information suggests that hepatocytes from appropriate rodent, and possibly other mammalian species, can be used to obtain metabolic activation in transformation assays that utilize cells with limited endogenous metabolic capabilities. On the basis of the available information, it appears that rat hepatocytes may be less suitable than hepatocytes from either mice or Syrian hamsters. In order to resolve these issues, it would be desirable to conduct a set of validation assays using: hepatocytes from several species, and possibly different mouse strains, a small selection of test chemicals from key chemical classes, and a reasonably facile and responsive assay system (BALB/c 3T3). This would provide the data needed to design one or more metabolic activation protocols for general use in screening transformation programs. In addition, the metabolic capacity of BALB/c 3T3 (3T3) cells to convert aniline-based amines to active carcinogens suggests that the application of genetic means to enhance the endogenous metabolic breadth of this or other cell strains, either by modulating control processes or adding genetic information, is a reasonable avenue of research.