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. 1977 Nov;36(5):558–563. doi: 10.1038/bjc.1977.231

A method for detecting carcinogenic organic chemicals using mammalian cells in culture.

J A Styles
PMCID: PMC2025395  PMID: 588420

Abstract

A method for testing organic chemicals for their carcinogenic potential is described. Baby hamster kidney cells (BHK-21/C1 13) were exposed to different doses of test compound in liquid tissue culture medium containing rat liver post-mitochondrial supernatant and cofactors (S-9 mix) to aid metabolism, but without serum. Survival of cells following exposure to the compound was assessed by cloning in liquid growth medium. Transformation was assessed by colony growth in semi-solid agar. The dose-response curve for survival was used to determine the LC50 of the compound. A dose-response curve for transformation was constructed and a 5-fold increase in transformation frequency at the LC50 was regarded as a positive test result. The method may also be used for testing gaseous compounds. Cells grown in monolayers and overlaid with serum-free medium and S-9 mix were exposed to vinyl chloride gas mixed with air. After exposure, the treated cells were trypsinized, resuspended in growth medium, and survival and transformation assays performed. The methods described are illustrated by examples taken from an evaluation study using 120 compounds and found to be more than 90% accurate in distinguishing between carcinogens and non-carcinogens.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
  2. Bartsch H., Malaveille C., Montesano R. Human, rat and mouse liver-mediated mutagenicity of vinyl chloride in S. typhimurium strains. Int J Cancer. 1975 Mar 15;15(3):429–437. doi: 10.1002/ijc.2910150309. [DOI] [PubMed] [Google Scholar]
  3. Bouck N., di Mayorca G. Somatic mutation as the basis for malignant transformation of BHK cells by chemical carcinogens. Nature. 1976 Dec 23;264(5588):722–727. doi: 10.1038/264722a0. [DOI] [PubMed] [Google Scholar]
  4. Creech J. L., Jr, Johnson M. N. Angiosarcoma of liver in the manufacture of polyvinyl chloride. J Occup Med. 1974 Mar;16(3):150–151. [PubMed] [Google Scholar]
  5. Di Mayorca G., Greenblatt M., Trauthen T., Soller A., Giordano R. Malignant transformation of BHK21 clone 13 cells in vitro by nitrosamines--a conditional state. Proc Natl Acad Sci U S A. 1973 Jan;70(1):46–49. doi: 10.1073/pnas.70.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evans C. H., DiPaolo J. A. Neoplastic transformation of guinea pig fetal cells in culture induced by chemical carcinogens. Cancer Res. 1975 Apr;35(4):1035–1044. [PubMed] [Google Scholar]
  7. Kirkland D. J., Armstrong C., Harris R. J. Spontaneous and chemically induced transformation of rat embryo cell cultures. Br J Cancer. 1975 Mar;31(3):329–337. doi: 10.1038/bjc.1975.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kirkland D. J., Pick C. R. The histological appearance of tumours derived from rat embryo cells transformed in vitro spontaneously and after treatment with nitrosomethylurea. Br J Cancer. 1973 Nov;28(5):440–452. doi: 10.1038/bjc.1973.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. MACPHERSON I., MONTAGNIER L. AGAR SUSPENSION CULTURE FOR THE SELECTIVE ASSAY OF CELLS TRANSFORMED BY POLYOMA VIRUS. Virology. 1964 Jun;23:291–294. doi: 10.1016/0042-6822(64)90301-0. [DOI] [PubMed] [Google Scholar]
  10. Maltoni C., Lefemine G., Chieco P., Carretti D. Vinyl chloride carcinogenesis: current results and perspectives. Med Lav. 1974 Nov-Dec;65(11-12):421–444. [PubMed] [Google Scholar]
  11. Mishra N. K., Di Mayorca G. In vitro malignant transformation of cells by chemical carcinogens. Biochim Biophys Acta. 1974 Dec 31;355(3-4):205–219. doi: 10.1016/0304-419x(74)90010-9. [DOI] [PubMed] [Google Scholar]
  12. Purchase I. F., Longstaff E., Ashby J., Styles J. A., Anderson D., Lefevre P. A., Westwood F. R. Evaluation of six short term tests for detecting organic chemical carcinogens and recommendations for their use. Nature. 1976 Dec 16;264(5587):624–627. doi: 10.1038/264624a0. [DOI] [PubMed] [Google Scholar]
  13. Umeda M., Iype P. T. An improved expression of in vitro transformation rate based on cytotoxicity produced by chemical carcinogens. Br J Cancer. 1973 Jul;28(1):71–74. doi: 10.1038/bjc.1973.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Viola P. L., Bigotti A., Caputo A. Oncogenic response of rat skin, lungs, and bones to vinyl chloride. Cancer Res. 1971 May;31(5):516–522. [PubMed] [Google Scholar]
  15. Wogan G. N., Paglialunga S., Archer M. C., Tannenbaum S. R. Carcinogenicity of nitrosation products of ephedrine, sarcosine, folic acid, and creatinine. Cancer Res. 1975 Aug;35(8):1981–1984. [PubMed] [Google Scholar]

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