Xeroderma pigmentosum is an autosomal recessive disease in which DNA repair processes are defective. All xeroderma piginentosum patients develop premature aging of sun-exposed skin, and some develop neurological abnormalities due to premature death of nerve cells. Sensitivity-to ultraviolet radiation of 24 xeroderma pigmentosum fibroblast strains was studied in vitro by measuring each strain's ability to divide and form colonies after irradiation. The most sensitive strains were derived from patients who had an early onset of neurological abnormalities; less sensitive strains were from patients with a later onset; and the most resistant strains were from patients without neurological abnormalities. The UV sensitivities of strains from each member of a sibling pair with xeroderma pigmentosum were identical, indicating that UV sensitivity of xeroderma pigmentosum strains is determined by the patient's inherited DNA repair defect. The results suggest that effective DNA repair is required to maintain the functional integrity of the human nervous system by preventing premature death of neurons. Cells from patients with xeroderma pigmentosum (XP), an autosomal recessive disease, have abnormal repair of DNA that has been damaged by ultraviolet (UV) radiation or certain chemical carcinogens (1). There are currently six known genetic forms of XP: the variant form, with a normal rate of UV-induced unscheduled DNA repair synthesis (a measure of excision repair) but abnormal postreplication repair (2), and five excision repair-deficient forms, which have been classified into complementation groups A-E by cell fusion of their strains (3). All XP patients develop excessive UV damage in sunlight-exposed areas at an early age. Some XP patients also develop neurological abnormalities due to the premature death of central nervous system neurons in the absence of recognizable and specific histopathology (1). We have, therefore, considered the neurological abnormalities of XP to be the result of an abnormal aging of the human nervous system (1).Post-UV colony-forming ability of human fibroblasts in vitro is markedly affected by the ability of the cells to repair their UV-damaged DNA to the functional state required for cell survival and division (4,5

Cockayne's syndrome is a form of cachectic dwarfism characterized by acute sun sensitivity and numerous other abnormalities of many organ systems. We studied fibroblasts from 9 Cockayne's syndrome patients to determine if their fibroblasts had abnormal post-ultraviolet light colony-forming ability or abnormal ultraviolet light-induced unscheduled DNA synthesis. The fibroblast strains from all the patients had markedly decreased post-ultraviolet light colony-forming ability in comparison with fibroblasts from control donors. Since this increased ultraviolet light sensitivity is propagable in vitro, it may be a manifestation of, or be closely associated with, the inherited genetic defect of this autosomal recessive disease. However, the patients' fibroblasts had normal rates of ultraviolet light-induced unscheduled DNA synthesis. Thus, unlike the UV sensitivity of DNA excision repair-deficient xeroderma pigmentosum strains, the UV sensitivity of Cockayne's syndrome strains is not related to abnormal DNA excision repair, at least to the extent that this repair process is reflected by rates of ultraviolet light-induced unscheduled DNA synthesis.

A simple, rapid, and reproducible test has been developed to measure the viability of cells after irradiation with ultraviolet light (UV). Epstein-Barr virus-transformed lymphoid lines, derived from patients with xeroderma pigmentosum (XP), were irradiated with UV, and the post-UV viability of the lymphoid lines was determined by the trypan blue dye exclusion method. The relative post-UV survival of the patients' lymphoid lines was similar to the relative post-UV survival of the patients' fibroblast strains.

No abstract