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Modulation of Induced Quantitative Mammalian Cell Transformation

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In Vitro Toxicity Testing of Environmental Agents

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Abstract

Cell strains can be used in a sensitive method for studying the process of carcinogenesis and are useful for identifying environmental agents that may be carcinogenic to humans. A wide range of organic and inorganic carcinogens are capable of inducing transformation. The inorganic metal salts include arsenic which is a known human carcinogen, although demonstration of its carcinogenicity in animals is lacking. The degree to which any agent-- a chemical, a virus, or irradiation-- transforms Syrian hamster cells and the extent to which one agent interacts with another from the same or a different category of carcinogens can be analyzed. Sequential treatment involving chemicals, viruses, and radiation are important, since combinations of various agents are probably responsible for an increased risk of cancer in human populations. The enhancement of chemical and viral transformation by chemicals is related to the length of chemical treatment and the interval between treatments. In chemical carcinogenesis, the mechanism of transformation enhancement by various agents is not associated with the rate of excision or post-replication repair in DNA, whereas the enhanced viral transformation by chemicals is related to additional sites for viral DNA attachment into cell DNA during repair of damaged DNA. Carcinogens affect a number of molecular processes of modify existing DNA and thus provide an explanation for carcinogenesis; in fact, in some systems some of these agents may also show mutagenic activity, and produce SCE and chromosomal aberrations. Quantitative approaches permit the study of dose-response relationships. The ability of the transformed cells to form tumors in animals makes mammalian cell models relevant to in vivo cancer studies. The in vitro results correlate well with results from life-time studies in mice and rats.

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References

  1. Alfred, L. J., and J. A. DiPaolo, 1968. Reversible inhibition of DNA synthesis in hamster embryo cells in culture: Action of 1,2-benzanthracene and 7,12-dimethylbenz(a)anthracene. Cancer Res., 28: 60–65.

    Google Scholar 

  2. Baetjer, A. M., 1950. Pulmonary carcinoma in chromate workers. I. A review of the literature and report of cases. Arch. Ind. Hyg. Occup. Med., 2: 487–516.

    Google Scholar 

  3. Berwald, Y., and L. Sachs, 1963.In vitro cell transformation with chemical carcinogens. Nature (London), 200:1182–1184.

    Google Scholar 

  4. Borek, C., and L. Sachs, 1966.In vitro transformation by X-irradiation. Nature (London), 210:276–278.

    Google Scholar 

  5. Brusick, D., F. Gletten, D. R. Jaggannath, and U. Weekes, 1976. The mutagenic activity of ferrous sulfate for Salmonella typhimurium. Mutat. Res., 38: 387.

    Google Scholar 

  6. Carrel, A., 1925. Essential characteristics of malignant cells. JAMA, 84: 157–158.

    Article  Google Scholar 

  7. Casto, B. C., W. J. Pieczynski, N. Janosko, and J. A. DiPaolo, 1976. Significance of treatment interval and DNA repair in the enhancement of viral transformation by chemical carcinogens and mutagens. Chem.-Biol. Interact., 13: 105–125.

    Article  Google Scholar 

  8. Chen, T. T., and C. Heidelberger, 1969. In vitro malignant transformation of cells derived from mouse prostate in the presence of 3-methyl-cholanthrene. J. Natl. Cancer Inst., 42: 915–925.

    Google Scholar 

  9. Coggin, J. H., Jr., 1969. Enhanced virus transformation of hamster embryo cells in vitro. J. Virol., 3: 458–462.

    Google Scholar 

  10. Cooper, W. C., 1976. Cancer mortality patterns in the lead industry. Ann. N.Y. Acad. Sci., 271: 255.

    Article  ADS  Google Scholar 

  11. Culter, S. J., and J. L. Young (eds.), 1975. Third national cancer survey: Incidence data. Natl. Cancer Inst. Monogr., 41: 1–454.

    Google Scholar 

  12. Diamond, L., and H. V. Gelboin, 1969. Alpha-naphthoflavone: An inhibitor of hydrocarbon cytotoxicity and microsomal hydroxylase. Science, 166: 1023–1025.

    Article  ADS  Google Scholar 

  13. DiPaolo, J. A., 1974. Quantitative aspects of in vitro chemical carcinogenesis, pp. 443–455. In: “Chemical Carcinogenesis,” Part B, P. 0. P. Ts’o and J. A. DiPaolo (eds.). Marcel Dekker, Inc., New York.

    Google Scholar 

  14. DiPaolo, J. A., 1975. Introductory remarks to formal symposium: carcinogenesis in vitro. Twenty-fifth annual meeting Tissue Culture Assoc., Inc. In Vitro, 11: 87–88.

    Google Scholar 

  15. DiPaolo, J. A., 1979. Quantitative transformation by carcinogens of cells in early passage. In: “Environmental Carcinogenesis,” P. Emmelot and E. Kriek (eds.). Elsevier/North- Holland Biomedical Press, Amsterdam.

    Google Scholar 

  16. DiPaolo, J. A., and B. C. Casto, 1979. Quantitative studies of in vitro morphological transformation of Syrian hamster cells by inorganic metal salts. Cancer Res., 39 1008–1013.

    Google Scholar 

  17. DiPaolo, J. A., and P. J. Dorlovan, 1976.In vitro morphologic transformation of Syrian hamster cells by UV-irradiation is enhanced by X-irradiation and unaffected by chemical carcinogens. Int. J. Radiat. Biol.,30 41–53.

    Google Scholar 

  18. DiPaolo, J. A,, and C. H. Evans, Unpublished results.

    Google Scholar 

  19. DiPaolo, J. A., J. Doniger, and A. DeMarinis, Unpublished data.

    Google Scholar 

  20. DiPaolo, J. A., R. L. Nelson, and P. J. Donovan, 1969. Sarcoma producing cell lines derived from clones transformed in vitro by benzo(a)pyrene. Science, 165: 917–918.

    Article  ADS  Google Scholar 

  21. DiPaolo, J. A., P. J. Donovan, and R. L. Nelson, 1971a. In vitro transformation of hamster cells by polycyclic hydrocarbons: Factors influencing the number of cells transformed. Nature (New Bio.), 230: 240–242.

    Google Scholar 

  22. DiPaolo, J. A., P. J. Donovan, and R. L. Nelson, 1971b. Transformation of hamster cells in vitro by polycyclic hydrocarbons without cytotoxicity. Proc. Natl. Acad. Sci. (USA), 68: 2958–296l

    Article  ADS  Google Scholar 

  23. DiPaolo, J. A., P. J. Donovan, and R. L. Nelson, 1971c. Transformation of hamster cells in vitro by polycyclic hydrocarbons without cytotoxicity. Proc. Natl. Acad. Sci. (USA), 68: 2958–2961.

    Article  ADS  Google Scholar 

  24. DiPaolo, J. A., P. J. Donovan, and R. L. Nelson, 1971d. X-irradiation enhancement of transformation by benzo(a)pyrene in hamster embryo cells. Proc. Natl. Acad. Sci. (USA), 68: 1734–1737.

    Article  ADS  Google Scholar 

  25. DiPaolo, J. A., K. Takano, and N. C. Popescu, 1972a. Quantitation of chemically induced neoplastic transformation of Balb/ 3T3 cloned cell lines. Cancer Res., 32 2686–2695.

    Google Scholar 

  26. DiPaolo, J. A., R. L, Nelson, and P. J. Donovan, 1972b. In vitro transformation of Syrian hamster embryo cells by diverse chemical carcinogens. Nature, 235:278–280.

    Google Scholar 

  27. DiPaolo, J. A., R. L. Nelson, P. J. Donovan, and C. H. Evans, 1973. Host-mediated in vivo-in vitro assay for chemical carcinogens. Arch. Pathol., 95: 380–385.

    Google Scholar 

  28. DiPaolo, J. A., P. J. Donovan, and B. C. Casto, 1974. Enhancement by alkylating agents of chemical carcinogen transformation of hamster cells in culture. Chem.-Biol. Interact., 9: 351–364.

    Article  Google Scholar 

  29. DiPaolo, J. A., R. L. Nelson, and B. C. Casto, 1978. In vitro neoplastic transformation of Syrian hamster cells by lead acetate and its relevance to environmental carcinogenesis. Br. J. Cancer, 38:452–455.

    Google Scholar 

  30. DiPaolo, J. A., P. J. Donovan, and N. C. Popescu, 1976. Kinetics of Syrian hamster cells during X-irradiation enhancement of transformation in vitro by chemical carcinogen. Radiat. Res., 66: 310–325.

    Article  Google Scholar 

  31. Doniger, J., and J. A. DiPaolo, 1980. Excision and post-replication DNA repair capacities, enhanced transformation, and survival of Syrian hamster embryo cells irradiated by ultraviolet light. Cancer Res.,; 40 (3): 582–587.

    Google Scholar 

  32. Donovan, P. J., and J. A. DiPaolo, 1974. Caffeine enhancement of chemical carcinogen-induced tranformation of cultured Syrian hamster cells. Cancer Res., 34: 2720–2727.

    Google Scholar 

  33. Earle, W. R., and A. Netleship, 1943. Production of malignancy in vitro. V. Results of injections of cultures into mice. J. Natl. Cancer Inst., 4: 213–227.

    Google Scholar 

  34. Evans, C. H., E. S. Rabin, and J. A. DiPaolo, 1977. The susceptibility of guinea pig cells to the colony inhibitory activity of lymphotoxin during carcinogenesis. Cancer Res., 37: 898–903.

    Google Scholar 

  35. Gart, J. J., J. A. DiPaolo, and P. J. Donovan, 1979. Mathematical models and the statistical analyses of cell transformation experiments. Cancer Res., 39 (12): 5069–5075.

    Google Scholar 

  36. Gelboin, H. V., F. Wiebel, and L. Diamond, 1970. Dimethylbenzanthracene tumorigenesis and aryl hydrocarbon hydroxylase in mouse skin: Inhibition by 7,8-benzoflavone. Science, 170: 169.

    Article  ADS  Google Scholar 

  37. Gey, G. O., 1941. Cytological and cultural observations on transplantable rat sarcomata produced by inoculation of altered normal cells maintained in continuous culture. Cancer Res., 1: 737.

    Google Scholar 

  38. Groth, D. H., L. Stettler, and G. Mackay, 1976. Interactions of mercury, cadmium, selenium, tellurium, arsenic, and beryllium, pp. 527–543. In: “Effects and Dose-Response Relationships of Toxic Metals,” G. F. Nordberg (ed.). Elsevier Scientific Publishing Co., Amsterdam.

    Google Scholar 

  39. Hernberg, S., 1977. Incidence of cancer in population with exceptional exposure to metals, pp. 147–153. In: “Origins of Human Cancer,” Book A, H. H. Hiatt, J. D. Watson, and J. A. Winsten (eds.). Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.

    Google Scholar 

  40. Huberman, E., and L. Sachs, 1966. Cell susceptibility to transformation and cytotoxicity by the carcinogenic hydrocarbon benzo(a)pyrene. Proc. Natl. Acad. Sci. (USA), 56 1123–1129.

    Article  ADS  Google Scholar 

  41. IARC, International Agency for Research on Cancer, 1973. IARC monographs on the evaluation of the carcinogenic risk of chemicals to man. Vol. 2. Some inorganic and organometallic compounds, pp. 17–47; 74–99; 126–149. IARC, Lyon.

    Google Scholar 

  42. Langard, S., and T. Norseth, 1975. A cohort study of bronchial carcinomas in workers producing chromate pigments. Br. J. Ind. Med., 32: 62–65.

    Google Scholar 

  43. Lee, A. M., and J. F. Fraumeni, Jr., 1969. Arsenic and respiratory cancer in man: An occupational study. J. Natl. Cancer Inst., 42 1045–1052.

    Google Scholar 

  44. Lofroth, G., and B. Maes, 1978. Mutagenicity of inorganic compounds in Salmonella typhimurium: arsenic, chromium, and selenium. Mutat. Res., 53: 65–66.

    Google Scholar 

  45. Myhr, B. C., and J. A. DiPaolo, 1975. Requirement of cell dispersion prior to selection of induced azaguanine-resistant colonies of Chinese hamster cells. Genetics, 80: 157–169.

    Google Scholar 

  46. Myhr, B. C., and J. A. DiPaolo, 1978a. Mutagenesis of Chinese hamster cells in vitro by combination treatment with methyl methane-sulfonate and N-acetoxy-2-acetylaminofluorene. Cancer Res., 38: 2539–2543.

    Google Scholar 

  47. Myhr, B. C., and J. A. DiPaolo, 1978b. Mutagenesis by N-acetoxy- 2-acetylfluorene of Chinese hamster V79 cells is unaffected by caffeine. Chem.-Biol. Interact., 21: 1–18.

    Article  Google Scholar 

  48. NIOSH, National Institute for Occupational Safety and Health, 1975. Criteria for a recommended standard: occupational exposure to inorganic arsenic new criteria, 1975. Publication #75149, U.S. Department of Health, Education, and Welfare, Rockville, Maryland.

    Google Scholar 

  49. Oshiro, Y., and J. A. DiPaolo, 1974. Changes in the uptake of 2- deoxy-D-glucose in Balb/3T3 cells chemically transformed in culture. J. Cell. Physiol., 83: 193–202.

    Article  Google Scholar 

  50. Popescu, N. C., S. C. Amsbaugh, and J. A. DiPaolo, 1979. The relevance of caffeine post-treatment of SCE incidence induced in Chinese hamster cells. Mutat. Res., 60: 313–320.

    Article  Google Scholar 

  51. Puck, T. T., P. I. Marcus, and S. J. Cieciura, 1956. Clonal growth of mammalian cells in vitro. Growth characteristics of colonies from single HeLa cells with and without a “feeder” layer. J. Exp. Med., 103: 273–284.

    Article  Google Scholar 

  52. Reitz, M. S., W. C. Saxinger, R. C. Ting, R. C. Gallo, and J. A. DiPaolo, 1977. Lack of expression of type-C hamster virus after neoplastic transformation of hamster embryo fibroblasts by benzo(a)pyrene. Cancer Res., 37: 3583–3589.

    Google Scholar 

  53. Sirover, M. A., and L. A. Loeb, 1976. Infidelity of DNA synthesis in vitro: Screening for potential metal mutagens or carcinogens. Science, 194: 1434–1436.

    Article  ADS  Google Scholar 

  54. Stoker, M., 1963. Effect of X-irradiation on susceptibility of cells to transformation by polyoma virus. Nature (London), 200: 756–758.

    Article  ADS  Google Scholar 

  55. Sunderman, F. W., Jr., 1976. A review of the carcinogenicities of nickel, chromium, and arsenic compounds in man and animals. Preventive Medicine, 5: 279–294.

    Article  Google Scholar 

  56. Sunderman, F. W., Jr., 1977. Metal carcinogenesis, pp. 257–295. In: “Advances in Modern Toxicology,” Vol. 1, R. A. Coyer and M. A. Mehlman (eds.). Hemisphere Publishing Corporation, Washington, D. C.

    Google Scholar 

  57. Wagoner, J. K., P. F. Infante, and T. Mancuso, 1978. Beryllium: Carcinogenicity studies. Science, 201: 298–303.

    Article  ADS  Google Scholar 

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Author information

Authors and Affiliations

  1. Laboratory of Biology, National Cancer Institute, Bethesda, Maryland, 20205, USA

    Joseph A. DiPaolo

  2. Division of Cancer Cause and Prevention, National Cancer Institute, Bethesda, Maryland, 20205, USA

    Joseph A. DiPaolo

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  1. Joseph A. DiPaolo
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Editors and Affiliations

  1. Research Triangle Institute, Research Triangle Park, North Carolina, USA

    Alan R. Kolber , Robert S. DeWoskin  & Thomas J. Hughes ,  & 

  2. National Institute of Environmental Health Sciences (BRAP), Research Triangle Park, North Carolina, USA

    Thomas K. Wong

  3. U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA

    Lester D. Grant

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© 1983 Plenum Press, New York

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DiPaolo, J.A. (1983). Modulation of Induced Quantitative Mammalian Cell Transformation. In: Kolber, A.R., Wong, T.K., Grant, L.D., DeWoskin, R.S., Hughes, T.J. (eds) In Vitro Toxicity Testing of Environmental Agents. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3566-5_15

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  • DOI: https://doi.org/10.1007/978-1-4613-3566-5_15

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  • Online ISBN: 978-1-4613-3566-5

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