Characterization of an epithelial, nearly diploid liver cell strain, from Chinese hamster, able to activate promutagens.
Epithelial liver cells of the Chinese hamster (CHEL cells) were propagated in culture for 35 passages. At favourable cell densities, the population doubling time in normal medium, was 20 h. L-Tyrosine amino transferase activity was retained at a measurable level, but its enhancement by dexamethasone was detected solely in cells of early passages. Pyruvate kinase was strongly activated by fructose-1,6-biphosphate at low substrate concentrations. These enzymatic properties suggest that the CHEL cells are derived from a sub-population of parenchymal hepatocytes or from cells closely related to parenchymal hepatocytes. With a lag period of a few hours, CHEL cultures metabolized benzo[a]pyrene. In cell homogenates the various monooxygenase activities investigated were below the detection limits. However, other xenobiotic-metabolizing activities, such as cytochrome P-450 reductase, glutathione transferase and UDP-glucuronosyl-transferase were high, with levels comparable to those observed in freshly isolated rat parenchymal cells. Epoxide hydrolase activity was also detected, but was lower than in the liver. The CHEL cells were able to activate benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene and aflatoxin B1 to mutagens, as shown in a co-culture assay with V79 cells, in which acquisition of resistance to 6-thioguanine was studied. At early passages, the CHEL cells had a near diploid set of chromosomes. Then, gradually the frequency of cells with slight changes in the number of chromosomes and the frequency of tetraploids were increased. During the observation period (up to passage 20) the modal number of chromosomes shifted from 22 to 23. No gross morphological changes in the cultures were noticed during the 20 passages.(ABSTRACT TRUNCATED AT 250 WORDS)
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001711:Biotransformation; D002455:Cell Division; D002478:Cells, Cultured; D002999:Clone Cells; D006224:Cricetinae; D003412:Cricetulus; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D007621:Karyotyping; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism; D014444:Tyrosine Transaminase / Q000378:metabolism
D000348:Aflatoxins; D009153:Mutagens; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D016604:Aflatoxin B1; D014444:Tyrosine Transaminase; D011770:Pyruvate Kinase