Unique cross-link and monoadduct repair characteristics of a xeroderma pigmentosum revertant cell line

Abstract

Monoadducts and cross-links formed in DNA of human cells by a psoralen derivative, 4′-hydroxy-methyl-4,5′,8-trimethylpsoralen (HMT), have been measured by a new, simple method, based on S₁ nuclease digestion of ³H-labeled adducts in DNA, that provides rapid information on the repair of both classes of lesions. Normal human fibroblasts and cells from patients with dyskeratosis congenita and xeroderma pigmentosum (XP) group C were capable of removing both monoadducts and cross-links, whereas XP groups A and D failed to remove either. An XP revertant, isolated from a group A cell line on the basis of an acquired mutagen-induced resistance to ultraviolet light, has the unique property of being capable of removing cross-links but not monoadducts. Consistent with this property, the XP revertant was found to be resistant to cell killing by the cross-linking psoralen derivative, HMT, but as sensitive as its parental cell line to a monofunctional psoralen derivative, 5-methylisopsoralen.