Psoralen photoinactivation of herpes simplex virus: monoadduct and cross-link repair by xeroderma pigmentosum and Fanconi's anemia cells.
Furocoumarins (psoralen and its derivatives) are used to photoinactivate a variety of viruses and cell types. In the presence of long-wavelength ultraviolet light (UVA), furocoumarins bind covalently with pyrimidine residues via a cyclobutane ring. A second photoevent allows pyrimidines located on the opposite DNA strand in an adjacent base pair to react, forming a cross-link. In the experiments in this report, psoralen photoinactivation is employed to investigate human DNA repair pathways by analyzing the ability of xeroderma pigmentosum (XP) and Fanconi's anemia (FA) cells to rescue psoraleninactivated herpes simplex virus (HSV). Comparison of several XP complementation groups and one XP variant with normal human fibroblasts demonstrates that the ability of all cells to repair damage by 4,5',8-trimethylpsoralen (TMP), a derivative that forms cross-links efficiently, is similar. However, HSV photochemically reacted with 5-methylangelicin (5-MA), an isopsoralen that forms only monoadducts, is repaired at significantly lower levels in several XP complementation groups than in control fibroblast cells, which indicates that the XP repair deficiency resides in the removal of monoadducts and not of cross-links in these cell lines. Surprisingly, the FA cells rescue both TMP- and 5-MA-treated virus with slightly greater efficiency than that observed in normal human fibroblasts.
D000741:Anemia, Aplastic / Q000382:microbiology*; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000627:therapeutic use*; D004260:DNA Repair / Q000187:drug effects*; D005199:Fanconi Anemia / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology*; D011564:Furocoumarins / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D011701:PUVA Therapy; D010778:Photochemotherapy; D018139:Simplexvirus / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014307:Trioxsalen / Q000627:therapeutic use; D014776:Virus Cultivation; D014983:Xeroderma Pigmentosum / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology*
D003432:Cross-Linking Reagents; D011564:Furocoumarins; C023026:5-methylangelicin; D014307:Trioxsalen