Tumorigenicity, oncogene transfection, and radiosensitivity

Cancer J Sci Am. Nov-Dec 1996;2(6):351-5.

Abstract

Purpose: Reports that the incorporation of exogenous oncogenes confer radioresistance have excited interest and controversy. We investigate whether human cell lines transformed to a malignant phenotype by gamma-rays or by chemicals became radioresistant.

Materials and methods: Rodent intestinal epithelial cells immortalized by the HPV virus, human immortalized bronchoepithelial cells and their malignant counterparts transformed by alpha-particles, uroepithelial cells and their malignant counterparts transformed either by alpha-particles or methylcholanthrine-4, and osteosarcoma cells and their nonmalignant counterparts into which the Rb gene had been introduced were used. Dose response curves for all of these cell lines were obtained by exposure to cesium 137 gamma-rays at a dose-rate of 1.18 Gy/min.

Results: There was a dramatic increase in resistance to gamma-rays when H-ras was transfected into rodent intestinal epithelial cells. By contrast, in the case of the three human cell lines used, no consistent or significant change of radiosensitivity occurred when normal cells were transformed to a malignant state by alpha-particles or by a chemical carcinogen.

Conclusions: Experiments involving the introduction of foreign oncogenes to cause tumorigenicity and accompanying radioresistance do not have direct relevance in human tumors. In a number of different instances, the conversion to malignancy by means that more closely reflect what happens in practice (i.e., by radiation or a chemical carcinogen) is not necessarily accompanied by an increased radioresistance to low doses of radiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alpha Particles
  • Animals
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / radiotherapy
  • Cell Transformation, Neoplastic* / drug effects
  • Cell Transformation, Neoplastic* / radiation effects
  • Cells, Cultured
  • Dose-Response Relationship, Radiation
  • Epithelial Cells / drug effects
  • Epithelial Cells / radiation effects
  • Gamma Rays
  • Genes, ras*
  • Humans
  • Intestines / drug effects
  • Intestines / radiation effects
  • Methylcholanthrene / pharmacology
  • Osteosarcoma / drug therapy
  • Osteosarcoma / radiotherapy
  • Radiation Tolerance / genetics*
  • Retinoblastoma Protein / pharmacology*
  • Transfection*
  • Urothelium / cytology
  • Urothelium / drug effects
  • Urothelium / radiation effects

Substances

  • Retinoblastoma Protein
  • Methylcholanthrene