Abe, S; Nemoto, N; Sasaki, M
The effects of 1,2-benz(a)anthracene (56553) (BaA) on aryl-hydrocarbon-hydroxylase (AHH) activity, and the effects of benzo(a)pyrene (50328) (BaP), 7,12-dimethylbenz(a)anthracene (57976) (DMBA), and 3-methylcholanthrene (56495) (MCA) on the inducibility of sister chromatid exchanges (SCEs), were studied in mammalian cell lines. Test chemicals were applied to cultured C-HC-4 and C-HC-20 human hepatomas, a rat ascites hepatoma, a rat esophageal tumor, and Chinese-hamster cells in unspecified doses. AHH assays and SCE analyses were carried out using the same cell line culture passages. Basal and induced AHH activity values were determined fluorometrically. Following induction by BaA, none of the three rodent cell lines tested exhibited an appreciable AHH activity increase, whereas the activity of this enzyme was increased by 140 and 64 times the basal value, respectively, in the C-HC-4 and C-HC-20 human hepatoma cells. BaP, DMBA, and MCA produced a 3 fold to 5 fold dose dependent SCE frequency increase in these human cell lines as compared to control values. While the three rodent cell lines exhibited an apparently dose dependent 2 fold to 3 fold SCE frequency increase following DMBA treatment, doses 10 to 100 times higher than those producing a similar effect in human cell lines were required. BaP and MCA produced SCE frequency increases of less than 2.5 and less than 1.8, respectively, in the rodent cell lines. The authors conclude that the human hepatoma cell lines tested are highly sensitive to DMBA, BaP and MCA, whereas the rodent cell lines investigated are only slightly or moderately sensitive to these chemicals. Enzymes other than AHH may be responsible for the metabolic conversion of polycyclic aromatic hydrocarbons to the DNA reactive forms capable of inducing SCEs in the rodent cell lines tested. SCE analysis is recommended for use in determining the genotoxicity of mutagens and carcinogens, and in testing the abilities of certain cell systems to metabolically activate mutagenic and carcinogenic chemicals.