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. We report here an extension of these studies in which we have examined the in vitro 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. Our data point to a metabolic anomaly which may contribute to the carcinogenic risk of the melanoma prone preneoplastic state presented by some DNS patients.
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000503:physiopathology*; D009506:Nevus / Q000503:physiopathology*; D009600:Nitroquinolines / Q000633:toxicity*; D011230:Precancerous Conditions / Q000503:physiopathology*; D012878:Skin Neoplasms / Q000503:physiopathology*; D013577:Syndrome
D009600:Nitroquinolines; D015112:4-Nitroquinoline-1-oxide