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. 1990 Aug;88:149–155. doi: 10.1289/ehp.9088149

Modulating factors in the expression of radiation-induced oncogenic transformation.

E J Hall 1, T K Hei 1
PMCID: PMC1567993  PMID: 2272310

Abstract

Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitative are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing alpha-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene.

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Selected References

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

  1. BERWALD Y., SACHS L. IN VITRO CELL TRANSFORMATION WITH CHEMICAL CARCINOGENS. Nature. 1963 Dec 21;200:1182–1184. doi: 10.1038/2001182a0. [DOI] [PubMed] [Google Scholar]
  2. Bertram J. S., Kolonel L. N., Meyskens F. L., Jr Rationale and strategies for chemoprevention of cancer in humans. Cancer Res. 1987 Jun 1;47(11):3012–3031. [PubMed] [Google Scholar]
  3. Borek C., Ong A., Mason H. Distinctive transforming genes in x-ray-transformed mammalian cells. Proc Natl Acad Sci U S A. 1987 Feb;84(3):794–798. doi: 10.1073/pnas.84.3.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Borek C., Sachs L. In vitro cell transformation by x-irradiation. Nature. 1966 Apr 16;210(5033):276–278. doi: 10.1038/210276a0. [DOI] [PubMed] [Google Scholar]
  5. Borek C. The induction and control of radiogenic transformation in vitro: cellular and molecular mechanisms. Pharmacol Ther. 1985;27(1):99–142. doi: 10.1016/0163-7258(85)90066-x. [DOI] [PubMed] [Google Scholar]
  6. Bos J. L. The ras gene family and human carcinogenesis. Mutat Res. 1988 May;195(3):255–271. doi: 10.1016/0165-1110(88)90004-8. [DOI] [PubMed] [Google Scholar]
  7. Dotto G. P., Parada L. F., Weinberg R. A. Specific growth response of ras-transformed embryo fibroblasts to tumour promoters. Nature. 1985 Dec 5;318(6045):472–475. doi: 10.1038/318472a0. [DOI] [PubMed] [Google Scholar]
  8. Erdstein J., Guyda H. J., Mishkin S. Effects of hypophysectomy and hormone replacement on the local and metastatic growth of Morris hepatoma 44. Cancer Res. 1984 Jul;44(7):2936–2941. [PubMed] [Google Scholar]
  9. Fusenig N. E., Dzarlieva-Petrusevska R. T., Breitkreutz D. Phenotypic and cytogenetic characteristics of different stages during spontaneous transformation of mouse keratinocytes in vitro. Carcinog Compr Surv. 1985;9:293–326. [PubMed] [Google Scholar]
  10. Guernsey D. L., Ong A., Borek C. Thyroid hormone modulation of X ray-induced in vitro neoplastic transformation. Nature. 1980 Dec 11;288(5791):591–592. doi: 10.1038/288591a0. [DOI] [PubMed] [Google Scholar]
  11. Harisiadis L., Miller R. C., Hall E. J., Borek C. A vitamin A analogue inhibits radiation-induced oncogenic transformation. Nature. 1978 Aug 3;274(5670):486–487. doi: 10.1038/274486a0. [DOI] [PubMed] [Google Scholar]
  12. Hei T. K., Hall E. J., Kushner S., Osmak R. S. Hyperthermia, chemotherapeutic agents and oncogenic transformation. Int J Hyperthermia. 1986 Jul-Sep;2(3):311–320. doi: 10.3109/02656738609016488. [DOI] [PubMed] [Google Scholar]
  13. Henderson B. E., Ross R. K., Pike M. C., Casagrande J. T. Endogenous hormones as a major factor in human cancer. Cancer Res. 1982 Aug;42(8):3232–3239. [PubMed] [Google Scholar]
  14. Hsiao W. L., Gattoni-Celli S., Weinstein I. B. Oncogene-induced transformation of C3H 10T1/2 cells is enhanced by tumor promoters. Science. 1984 Nov 2;226(4674):552–555. doi: 10.1126/science.6436974. [DOI] [PubMed] [Google Scholar]
  15. Kakunaga T. A quantitative system for assay of malignant transformation by chemical carcinogens using a clone derived from BALB-3T3. Int J Cancer. 1973 Sep 15;12(2):463–473. doi: 10.1002/ijc.2910120217. [DOI] [PubMed] [Google Scholar]
  16. Komatsu K., Miller R. C., Hall E. J. The oncogenic potential of a combination of hyperthermia and chemotherapy agents. Br J Cancer. 1988 Jan;57(1):59–63. doi: 10.1038/bjc.1988.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  18. Lotan R. Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta. 1980 Mar 12;605(1):33–91. doi: 10.1016/0304-419x(80)90021-9. [DOI] [PubMed] [Google Scholar]
  19. Milo G. E., Jr, DiPaolo J. A. Neoplastic transformation of human diploid cells in vitro after chemical carcinogen treatment. Nature. 1978 Sep 14;275(5676):130–132. doi: 10.1038/275130a0. [DOI] [PubMed] [Google Scholar]
  20. Reznikoff C. A., Bertram J. S., Brankow D. W., Heidelberger C. Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division. Cancer Res. 1973 Dec;33(12):3239–3249. [PubMed] [Google Scholar]
  21. Reznikoff C. A., Loretz L. J., Christian B. J., Wu S. Q., Meisner L. F. Neoplastic transformation of SV40-immortalized human urinary tract epithelial cells by in vitro exposure to 3-methylcholanthrene. Carcinogenesis. 1988 Aug;9(8):1427–1436. doi: 10.1093/carcin/9.8.1427. [DOI] [PubMed] [Google Scholar]

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