Cooperation between human cells sensitive to UVA radiations: a clue to the mechanism of cellular hypersensitivity associated with different clinical conditions.
Six fibroblast strains sensitive to long wavelength ultraviolet radiation (UVA) and one control strain were used to see if cooperation between the different cell strains could modify the abnormally high yield of single-strand DNA breaks (SSB) in the sensitive strains caused by UVA irradiation in complete Dulbecco's MEM. The sensitive strains were established from individuals showing proneness to different types of light-induced skin damage (actinic reticuloid, familial actinic keratoses with internal malignancies, and unusual frequency of basal cell carcinomata). When sensitive and normal cells were cocultivated, the UVA-induced SSB decreased in the sensitive cells and increased in the normal ones by amounts proportional to the ratio of the two types of cells in the mixtures. Furthermore the regression of SSB, in the sensitive cells, on the proportion of normal cells in the mixture extrapolated to normal levels of SSB when the proportion of normal cells increased to one. Cocultivation of different sensitive cells did not reduce the UVA-induced SSB to levels below those of the less sensitive cell strains. From these results we conclude that substances, present in limiting amounts, even in normal cells, can be transferred from cell to cell, presumably by metabolic cooperation, and modify the yield of SSB caused by UVA radiation. The abnormal yields of SSB in the sensitive cells appear to be entirely attributable to deficits in the substances responsible for the intercellular cooperation. We suggest that such substances are small molecular weight scavengers of active oxygen species.
Francis
A J
AJ
Division of Medical & Molecular Genetics, United Medical School, Guy's Hospital, London Bridge, London.
Giannelli
F
F
D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D066298:In Vitro Techniques; D010787:Photosensitivity Disorders / Q000235:genetics* / Q000473:pathology; D012044:Regression Analysis; D014466:Ultraviolet Rays
D004247:DNA