Search

Many short-term carcinogen-screening assays use transformed cells which require exogenous metabolizing systems to activate carcinogens. We have sought un-transformed target cell-lines with a high mitotic index and the intrinsic ability to metabolize carcinogens. Hybrid cell clones were established by fusing an un-transformed 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. [ABSTRACT FROM PUBLISHER]

A cloned, untransformed rat liver cell-line, LNRL (with the normal diploid karyotype and epithelial morphology) was tested for use as the metabolizing component in a co-cultivation system for carcinogen-screening using sister chromatid exchanges (SCE) as the criterion. The well characterized early cultures of LNRL cells were co-cultivated with Chinese hamster ovary (CHO) cells, the target commonly used for the induction of SCE, and exposed to different concentrations of various chemicals for 24 h. Two poly-cyclic hydrocarbons, 7, 12-dimethylbenz[a]anthra-cene and benzo[a]pyrene did not produce any SCE in CHO cells cultured alone, but produced a significant number of SCE in CHO co-cultivated with LNRL. The aromatic amine, 2-acetylaminofluorene, and the potent carcinogenic mycotoxin, afiatoxin B, induced SCE to a limited extent even in CHO cells cultivated alone, but in the presence of liver cells the SCE frequency was greatly increased. Aflatoxin G, the least potent of the aflatoxins, also produced a response in the co-cultivation system. These results indicate that cultured liver cells can be used as the metabolizing cells in co-cultivation systems for carcinogen-screening. The advantages of this assay over those employing liver microsomal fractions are discussed. [ABSTRACT FROM PUBLISHER]