DNA-REPAIR IN HUMAN-CELLS CONTAINING PHOTOADDUCTS OF 8-METHOXYPSORALEN OR ANGELICIN

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (3) , 696-702
Abstract
Photoactivated 8-methoxypsoralen (8-MOP) was proven to be clinically effective for a number of dermatological conditions, including lichen planus, mycosis fungoides and psoriasis. 8-MOP forms 2 types of covalent photoproducts with DNA, monoadducts and bifunctional adducts which cross-link the 2 DNA strands. Angelicin is a congener of 8-MOP which forms only monoadducts. The combined density and isotopic labeling technique was used to study repair replication in cultured human fibroblasts treated with these compounds and exposed to near-UV light. In human diploid fibroblasts (WI-38), the time course of repair replication for both compounds is similar. Drug concentration and UV dose responses are also similar for 8-MOP and angelicin. No repair replication was stimulated by either compound in xeroderma pigmentosum cells from complementation group A (XP12BE). Apparently, repair replication in response to 8-MOP is primarily a response to monoadducts and the enzymatic pathway for this repair synthesis shares at least 1 step with the pathway for repair of pyrimidine dimers. Cross-link persistence in treated cells was assayed using the single-strand-specific S1 nuclease to digest DNA that did not renature readily following heat denaturation. Partial removal of cross-links was observed in normal, xeroderma pigmentosum variant and Fanconi''s anemia fibroblasts, but not in xeroderma pigmentosum Group A cells. [Evidence indicating that 8-MOP is a carcinogen is discussed.].

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