Abnormal Responses to Mid-Ultraviolet Light of Cultured Fibroblasts from Patients with Disorders Featuring Sunlight Sensitivity¹

We have examined the postultraviolet light (UV) colony-forming ability and DNA repair properties of human skin fibroblasts derived from two groups of donors at high risk of cancer: (a) persons exhibiting sensitivity to sunlight; and (b) persons with conditions possibly associated with an underlying defect in the repair of radiogenic DNA damage. A comparison has been made between the effects of far UV (254 nm) and mid UV (313 nm). The former is a well-studied but environmentally irrelevant carcinogen whereas the latter is a sparsely studied but environmentally relevant carcinogen. Relative to control strains from clinically normal donors, one strain in the first group, from a photosensitive dermatomyositic patient with basal cell carcinoma, displayed increased sensitivity to 313-nm light alone. The other strains surveyed in the first group (the two xeroderma pigmentosum strains and the one Bloom's syndrome strain) were hypersensitive to both UV wavelengths. In the second group of disorders, the strains showed three types of responses: (a) hypersensitivity to 313-nm UV but not 254-nm UV (two of four ataxia telangiectasia strains); (b) hypersensitivity to both 313-nm UV and 254-nm UV (one of five Fanconi's anemia strains); and (c) normal sensitivity at both wavelengths (both Rothmund-Thomson syndrome strains, the remaining four Fanconi's anemia strains, the remaining two ataxia telangiectasia strains, the one hereditary retinoblastoma, and the one ataxia telangiectasia heterozygote strain). Biochemical studies performed on strains sensitive to 313-nm UV alone suggest that their unusual photoresponse is not attributable to defective repair of cyclobutyl pyrimidine dimers. Furthermore, our data imply that thymine glycols are unlikely candidates for the critical lethal lesions in 313-nm UV-sensitive strains. Evidence is presented in support of the contention that mid UV may be partially radiomimetic, thus extending our understanding of the deleterious biological effects of this ubiquitous environmental carcinogen.