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

Carcinogenesis
P J SmithM C Paterson

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...Continue Reading

Citations

Oct 1, 1988·Cancer Genetics and Cytogenetics·F Hecht, B K Hecht
Apr 1, 1989·Mutation Research·R MirzayansM C Paterson
Jan 1, 1991·Toxicology in Vitro : an International Journal Published in Association with BIBRA·K A BlackJ W Grisham
Oct 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·M H GreeneS Rowe
Feb 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·J N HowellJ J McCormick
Aug 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R ParshadG M Jones
Jan 1, 1984·Journal of Cellular Physiology. Supplement·M C PatersonM Weinfeld
Jan 1, 1984·Hospital Practice·M H Greene
Jan 1, 1985·Clinics in Dermatology·C J Witkop

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