Induction of sister chromatid exchanges by carcinogens mediated through cultured rat liver epithelial cells.
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 polycyclic hydrocarbons, 7,12-dimethylbenz[a]anthracene 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, aflatoxin B1, 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 G2, 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.
Ray-Chaudhuri
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Chemical Carcinogenesis Program, NCI Frederick Cancer Research Center, MD 21701, USA.
Kelley
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D015073:2-Acetylaminofluorene / Q000493:pharmacokinetics / Q000633:toxicity; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics / Q000633:toxicity; D001973:Bromodeoxyuridine / Q000494:pharmacology; D016466:CHO Cells / Q000166:cytology / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D002460:Cell Line; D018920:Coculture Techniques; D006224:Cricetinae; D004847:Epithelial Cells / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009183:Mycotoxins / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011917:Rats, Inbred Lew; D012854:Sister Chromatid Exchange
D000963:Antimetabolites; D002273:Carcinogens; D009183:Mycotoxins; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D015073:2-Acetylaminofluorene; D001973:Bromodeoxyuridine