Cellular toxicity in Chinese hamster ovary cell cultures. I. Analysis of cytotoxicity endpoints for twenty-nine priority pollutants.
Chinese hamster ovary cells were exposed to 29 toxic chemical substances which were representative of several classes of compounds listed by the Natural Resources Defense Council Consent Decree as priority toxic pollutants. After cell cultures were exposed to the test substance, cell samples were assayed for protein and DNA synthesis, ATP, cell number, and viability. A filter-disk technique employing a batch-washing procedure was used for the determination of protein and DNA synthesis. Dose-response data were obtained for 15 of the more toxic agents including chlorinated aromatics, metallic compounds, phenols, and polychlorinated biphenyls. Estimates of the sample concentrations necessary to produce a 50% reduction in response were used to compare cytotoxicity endpoints. ATP and protein synthesis were approximately equally effective as indicators of cellular toxicity. Cadmium chloride, nickel nitrate, arsenic trioxide, and potassium chromate produced a more pronounced effect on DNA synthesis than on ATP or protein synthesis. The dose-response relationship for protein and DNA synthesis was a smooth, continuous function for responses as low as 1 to 2% of the control. On a log-log scale, the dose-response relation yielded a unique pattern for several chemical classes. A ranking of the compounds based on their inhibition of DNA synthesis was compared to a ranking obtained from the literature for whole-animal toxicity. With the exception of the polychlorinated biphenyls, the in vitro results correlated well with animal test data.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D010053:Ovary; D014176:Protein Biosynthesis
D004785:Environmental Pollutants; D000255:Adenosine Triphosphate; D004247:DNA