Enhanced G2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture
A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containing the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation.
- Research Organization:
- National Cancer Institute, Bethesda, MD
- OSTI ID:
- 6572531
- Journal Information:
- Cancer Res.; (United States), Vol. 5
- Country of Publication:
- United States
- Language:
- English
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CHROMATIDS
RADIOSENSITIVITY
EPIDERMIS
NEOPLASMS
NITROSO COMPOUNDS
CARCINOGENESIS
TUMOR CELLS
CELL PROLIFERATION
CARCINOGENS
CELL CULTURES
CELL CYCLE
CELL TRANSFORMATIONS
DNA REPAIR
KERATIN
MICE
ONCOGENES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
DISEASES
EPITHELIUM
GENES
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PROTEINS
RECOVERY
REPAIR
RODENTS
SCLEROPROTEINS
SKIN
TISSUES
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
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560300 - Chemicals Metabolism & Toxicology