Human epidermal keratinocytes retain radiation resistance following in vitro immortalization and malignant transformation
Journal Article
·
· Radiat. Res.; (United States)
The radiobiology of human tumors suggests that multiple factors are involved in clinical radioresponsiveness. To date, no direct experimental evidence is available to correlate intrinsic cellular radiosensitivity with the steps of malignant transformation. We developed an in vitro multistage model of epithelial neoplasia using human epidermal keratinocytes to examine the effects of malignant transformation on radiation response. These cells were first immortalized as a result of infection with a hybrid virus (adenovirus 12 and simian virus 40) and subsequently transformed either by infection with a second virus (Kirsten murine sarcoma virus) or by treatment with a chemical carcinogen (N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide). We demonstrate that primary human epidermal keratinocytes were radiation resistant (D0 = 2.24 Gy) as compared with human fibroblasts (D0 = 1.45 Gy) and that this resistance was retained in the immortalized as well as the transformed cell lines. These findings present direct experimental evidence that radiation sensitivity of malignant human keratinocytes is an intrinsic property of the precursor cell that may be conserved through the stages of neoplastic transformation.
- Research Organization:
- Georgetown Univ. School of Medicine, Washington, DC
- OSTI ID:
- 5840338
- Journal Information:
- Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 111:3; ISSN RAREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300 -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL ADAPTATION
BIOLOGY
BODY
CARCINOGENESIS
CELL TRANSFORMATIONS
CONNECTIVE TISSUE CELLS
DISEASES
EPIDERMIS
EPITHELIUM
FIBROBLASTS
IN VITRO
MAMMALS
MAN
MICROORGANISMS
NEOPLASMS
NITRO COMPOUNDS
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PARASITES
PATHOGENESIS
PRIMATES
RADIOBIOLOGY
RADIOSENSITIVITY
SKIN
SOMATIC CELLS
TISSUES
VERTEBRATES
VIRUSES
Cells
& Tissue Culture
560300 -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL ADAPTATION
BIOLOGY
BODY
CARCINOGENESIS
CELL TRANSFORMATIONS
CONNECTIVE TISSUE CELLS
DISEASES
EPIDERMIS
EPITHELIUM
FIBROBLASTS
IN VITRO
MAMMALS
MAN
MICROORGANISMS
NEOPLASMS
NITRO COMPOUNDS
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PARASITES
PATHOGENESIS
PRIMATES
RADIOBIOLOGY
RADIOSENSITIVITY
SKIN
SOMATIC CELLS
TISSUES
VERTEBRATES
VIRUSES