RESUMEN
Basal Cell Nevus Syndrome (BCNS) is a rare autosomal-dominant inherited disorder associated with a marked hypersusceptibility to spontaneous and radiation-induced skin cancer. We examined the changes in cell survival, unscheduled DNA synthesis (UDS) and the frequency of sister chromatid exchanges (SCE) induced by ultraviolet light (UVL) in confluent normal and BCNS fibroblasts. BCNS cells appeared slightly hypersensitive to the cytotoxic effects of UVL. The rate of UDS induced by UVL exposure in normal cell strains increased linearly following doses up to 30 J/m2, whereas in BCNS cells UDS became saturated at doses of 10 J/m2 showing no further increase with doses up to 30 J/m2. UDS activity persisted for longer periods after UVL exposure in BCNS as compared with normal cells. The dose-response relationship for UVL-induced SCE was similar in normal and BCNS fibroblasts. However, the frequencies of UVL-induced SCE declined to near background levels in normal cells following 12-24 hr of confluent holding prior to subculture whereas they remained elevated in BCNS cells with holding times up to 24 hr after UVL exposure. Overall, these results suggest that BCNS fibroblasts may have a diminished capacity for the repair of some type of DNA damage as compared with normal fibroblasts.
Asunto(s)
Síndrome del Nevo Basocelular/genética , Carcinoma Basocelular/genética , Rayos Ultravioleta , Adulto , Supervivencia Celular/efectos de la radiación , Niño , ADN/biosíntesis , Relación Dosis-Respuesta en la Radiación , Femenino , Fibroblastos/efectos de la radiación , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , Intercambio de Cromátides Hermanas/efectos de la radiaciónRESUMEN
A skin fibroblast cell strain (GM2995) derived from a patient with xeroderma pigmentosum was received at low passage. As the cells were serially passaged (1:4 dilution), their size and growth characteristics changed. By passage 13, approximately 90% of the colonies produced by cells seeded at low density were composed of small, densely packed cells. Cells capable of anchorage-independent growth were observed after passage 7; they formed round, smooth-edged colonies in soft agar. The frequency of cells exhibiting anchorage-independent growth increased rapidly at subsequent passages, reaching 35-50% of the population by passage 20. This phenomenon was accompanied by the appearance of aneuploidy. These cells are still proliferating actively at passage 35. These late-passage GM2995 cells retain the extreme hypersensitivity to the cytotoxic effect of UV radiation characteristic of early-passage GM2995 cells.