Asunto(s)
Línea Celular , Animales , Callitrichinae , Células Cultivadas , Técnicas Citológicas , HumanosAsunto(s)
Deleción Cromosómica , Inversión Cromosómica , Mapeo Cromosómico , Mutación , Células Cultivadas , Bandeo Cromosómico , Humanos , New JerseyAsunto(s)
Células Cultivadas , Variación Genética , Xerodermia Pigmentosa/genética , Adulto , Anciano , Reparación del ADN , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The "pigmented xerodermoid" was previously defined on the basis of mild clinical symptoms that suggested it might be similar to but distinct from xeroderma pigmentosum (XP). XP and pigmented xerodermoid cell cultures were irradiated with ultraviolet light and unscheduled DNA synthesis, strand breakage during repair, chain growth during semiconservative DNA replication with or without caffeine, and the recovery of DNA replication were determined. It is concluded that a pigmented xerodermoid cell culture is indistinguishable from the XP variant and the former term is therefore redundant. The defect common to these cell types appears to be the loss of a gene product that permits normal cells to replicate DNA without interruption at damaged sites (u.v.-induced pyrimidine dimers). The consequence of this loss is that replication forks are blocked more frequently and at lower doses in XP variant cells. The correlation between this defect and high levels of actinic carcinogenesis in these patients points to an important role for perturbations in DNA replication in human carcinogenesis.
Asunto(s)
Reparación del ADN/genética , Replicación del ADN/genética , Trastornos de la Pigmentación/genética , Xerodermia Pigmentosa/genética , Adolescente , Adulto , Antimetabolitos/farmacología , Cafeína/farmacología , Células Cultivadas/efectos de los fármacos , Células Cultivadas/efectos de la radiación , Citarabina/farmacología , Daño del ADN , Reparación del ADN/efectos de los fármacos , Reparación del ADN/efectos de la radiación , Replicación del ADN/efectos de los fármacos , Replicación del ADN/efectos de la radiación , Humanos , Masculino , Trastornos de la Pigmentación/clasificación , Trastornos de la Pigmentación/patología , Origen de Réplica/efectos de los fármacos , Factores de Tiempo , Rayos Ultravioleta , Xerodermia Pigmentosa/patologíaRESUMEN
Xeroderma pigmentosum (XP) has been reported to be unusually frequent among Middle Eastern populations. This report describes the first survey of DNA repair characteristics among Egyptians. Sixteen XP patients were contacted, and biopsies from eight were analyzed for unscheduled DNA synthesis, strand breakage during pyrimidine dimer excision, and complementation groups. The patients were equally distributed between Complementation Groups A and C. Unscheduled synthesis and strand breaks were significantly higher in Group C than in Group A cells. Central nervous system disorders were found in all of the Group A patients and in none of the Group C patients. No clinical symptoms were observed in the heterozygotes. A 2-month-old sib of an XP patient was free of symptoms, but unscheduled synthesis and strand breakage in cultures from this sib were the same as in the related XP homozygote. From the relative frequencies of each complementation group found in various parts of the world, we offer a hypothesis concerning the relative sizes and roles for gene products specified by the alleles or genes corresponding to each complementation group.