Sensitivity of a hamster lung cell line to direct and indirect acting carcinogens.
Cytotoxicity of benzo(a)pyrene (B(a)P), 7,12-dimethylbenz(a)anthracene (DMBA), aflatoxin B1 (AB1), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was estimated in vitro by using a hamster lung cell line. The studies were conducted to assess the usefulness of an organ-specific cell culture system for demonstrating differences in the cytotoxic potency of diverse chemical carcinogens. Cytotoxicity was determined by using the succinate dehydrogenase assay (MTT assay) after different incubation times and concentrations with the corresponding carcinogens. The effective concentration EC50 as well as the slope of the regression line were used as parameters for the biological effects. The results from these studies indicate a clear dose-dependent reaction after incubation of the cells with aflatoxin B1 (EC50: 2.3 microM) and MNNG (EC50: 4.0 microM). For the polycyclic hydrocarbons benzo(a)pyrene and DMBA, a dose-independent reaction was found. These results indicate that consideration of the EC50 values only might not be sufficient to characterize differences in the cytotoxic activity of different substances. Chemicals can lead to equal values in the EC50, but cells can differ significantly in their biological sensitivity, meaning that the extent of reduction in cell proliferation depends on the chemical used. By considering the two above-mentioned parameters, a ranking for the analyzed substances will be possible in the following way: AB1, MNNG, DMBA and B(a)P. Taken together, our experiments show that it is possible to reveal differences in the cytotoxic potency of chemicals by using in vitro methods.
Hilger
I
I
Institute of Experimental Pathology, Hannover Medical School, Germany.
Aufderheide
M
M
Knebel
J W
JW
Fuchs
S
S
Emura
M
M
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects; D008168:Lung / Q000737:chemistry* / Q000187:drug effects; D013385:Succinate Dehydrogenase / Q000032:analysis*
D002273:Carcinogens; D013385:Succinate Dehydrogenase