The use of liver epithelial cultures for the study of chemical carcinogenesis.

Liver cultures offer several special advantages for the study of chemical carcinogenesis in cell culture; these include the sensitivity of the cells to procarcinogens requiring enzymatic activation, the epithelial nature of the cells which qualifies them as a model for epithelial carcinogenesis, and the opportunity to compare culture findings with the extensive information available on the effects of carcinogens on liver. The actions of chemical carcinogens have been studied in primary and long-term rat liver cell cultures. A variety of procarcinogens induced DNA repair in primary cultures, indicating the usefulness of this system for studying carcinogen metabolism, the interaction of carcinogens with DNA, and the repair of carcinogen-induced DNA damage. In addition, this system may provide a screen for chemical carcinogens in which metabolic activation occurs in the target cell. Carcinogen treatment of long-term cultures initiated from the primary cultures resulted in morphologic transformation accompanied by an increased growth in soft agar and an increased frequency of 8-azaguanine-resistant mutants. Cultures with a high fraction of cells in S phase were found to be most sensitive to the induction of 8-azaguanine-resistant mutants.