Hybrid clones of rat liver and hamster ovary cells as targets for carcinogen screening.

Abstract

Many short-term carcinogen-screening assays use transformed cells which require exogenous metabolizing systems to activate carcinogens. We have sought untransformed target cell-lines with a high mitotic index and the intrinsic ability to metabolize carcinogens. Hybrid cell clones were established by fusing an untransformed rat liver cell-line (with a normal diploid karyotype, epithelial morphology and carcinogen-metabolizing capacity) and a Chinese hamster ovary cell-line (with a high mitotic index, ability to grow in soft agar, a characteristic of transformed cells, and which cannot metabolize most carcinogens). A number of such clones were characterized with respect to their morphology, karyology, growth properties and the ability to metabolize 7,12-dimethylbenz[a]anthracene. Selected hybrid clones were found to respond to several types of carcinogen, using the induction of sister chromatid exchange as the criterion. A significant increase in the induction was observed in cloned hybrid cell-lines compared with the hamster ovary cell line. Moreover, the same hybrid clones can be used repeatedly without an exogeneous activating system, which makes this test system very practical.