Abnormal responses to the carcinogen 4-nitroquinoline 1-oxide of cultured fibroblasts from patients with dysplastic nevus syndrome and hereditary cutaneous malignant melanoma
The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). A putative role of host-environmental interactions in the etiology of hereditary melanoma has been strengthened by the recent finding that fibroblasts derived from HCMM/DNS patients demonstrated enhanced sensitivity to u.v.-irradiation in vitro. An extension of these studies is reported in which we have examined the invitro responses to a model environmental carcinogen, 4-nitroquinoline 1-oxide (4NQO), of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. Three of the six HCMM/DNS strains showed enhanced cell killing with sensitivities greater than that of a xeroderma pigmentosum (XP) variant strain but less than those of ataxia telangiectasia and XP Group D cell strains. The inhibition and recovery of de novo DNA synthesis, together with the expression of repair synthesis, following 4NQO exposure appeared to be normal in HCMM/DNS strains, irrespective of their subsequent clonogenic potential. The data point to a metabolic anomaly which may contribute to the carcinogenic risk of the melanoma prone preneoplastic state presented by some DNS patients.
- Research Organization:
- Chalk River Nuclear Laboratories, Ontario
- OSTI ID:
- 6208111
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Vol. 4:7
- Country of Publication:
- United States
- Language:
- English
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FIBROBLASTS
RADIOSENSITIVITY
HEREDITARY DISEASES
ETIOLOGY
MELANOMAS
NITRO COMPOUNDS
BIOLOGICAL EFFECTS
QUINOLINES
ULTRAVIOLET RADIATION
CELL KILLING
DNA REPAIR
DNA REPLICATION
METABOLISM
PATIENTS
ANIMAL CELLS
AROMATICS
AZAARENES
AZINES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CONNECTIVE TISSUE CELLS
DISEASES
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
NEOPLASMS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIDINES
RADIATIONS
RECOVERY
REPAIR
SOMATIC CELLS
560306* - Chemicals Metabolism & Toxicology- Man- (-1987)
560121 - Radiation Effects on Cells- External Source- (-1987)