Fibroblasts from patients with hereditary cutaneous malignant melanoma are abnormally sensitive to the mutagenic effect of simulated sunlight and 4-nitroquinoline 1-oxide
Because of a possible etiologic link between mutations and carcinogenesis, the authors compared fibroblasts derived from skin biopsies of several patients with hereditary cutaneous malignant melanoma and the dysplastic nevus syndrome for sensitivity to the mutagenic and/or cytotoxic effect of broad-spectrum simulated sunlight and of a UV mimetic carcinogen, 4-nitroquinoline 1-oxide (4NQO). The genetic marker was resistant to 6-thioguanine; loss of colony-forming ability was the assay for cytotoxicity. All five strains tested were more sensitive than normal to the killing effect of 4NQO (slopes of survival curves were 2- to 3-fold steeper), but only one strain was hypersensitive to killing by Sun Lamp radiation. Two strains were tested for mutagenicity. The response of each to the mutagenic action of these agents corresponded to its response to cell killing. Both strains were hypermutable after exposure to 4NQO, but only one showed a higher than normal frequency of mutants induced by simulated sunlight. The finding that nonmalignant fibroblasts from patients with a hereditary variant of malignant fibroblasts from patients with a hereditary variant of malignant melanoma are abnormally susceptible to carcinogen-induced mutations suggests that hypersensitivity to mutagens contributes to risk of melanoma in patients. It also supports the somatic cell mutation hypothesis for the origin of cancer. 46 references, 3 figures.
- Research Organization:
- Michigan State Univ., East Lansing, MI (United States)
- OSTI ID:
- 5831459
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 81:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
FIBROBLASTS
SENSITIVITY
NITRO COMPOUNDS
MUTAGENESIS
ULTRAVIOLET RADIATION
BIOLOGICAL MARKERS
BIOPSY
CARCINOGENESIS
CELL KILLING
DNA REPAIR
EXPERIMENTAL DATA
HEREDITARY DISEASES
MELANOMAS
PATIENTS
TOXICITY
ANIMAL CELLS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CONNECTIVE TISSUE CELLS
DATA
DIAGNOSTIC TECHNIQUES
DISEASES
ELECTROMAGNETIC RADIATION
INFORMATION
NEOPLASMS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
RADIATIONS
RECOVERY
REPAIR
SOMATIC CELLS
560161* - Radionuclide Effects
Kinetics
& Toxicology- Man
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)