Abnormal responses to the carcinogen 4-nitroquinoline 1-oxide of cultured fibroblasts from patients with dysplastic nevus syndrome and hereditary cutaneous malignant melanoma.

Abstract:

: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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Smith PJ,Greene MH,Adams D,Paterson MC

doi

10.1093/carcin/4.7.911

subject

Has Abstract

pub_date

1983-01-01 00:00:00

pages

911-6

issue

7

eissn

0143-3334

issn

1460-2180

journal_volume

4

pub_type

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