Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied DNA repair in cultured mammalian cells treated with the furocoumarins 8-methoxypsoralen (8-MOP), aminomethyl trioxsalen, or angelicin and irradiated with near UV light. The amount of DNA cross-linked by 8-MOP in normal human cells decreased by about one-half in 24 hours after treatment; no decrease was observed in xeroderma pigmentosum cells, group A. At present, it is not known to what extent this decrease represents complete repair events at the sites of cross-links. Furocoumarin adducts elicited excision repair in normal human and monkey cells but not in xeroderma pigmentosum group A cells. This excision repair resembled in several aspects that elicited by pyrimidine dimers, formed in DNA by irradiation with 254-nm UV light; however, it appeared that for at least 8-MOP and aminomethyl trioxsalen, removal of adducts was not as efficient as was the removal of pyrimidine dimers. We also compared repair in the 172-base-pair repetitive alpha-DNA component of monkey cells to repair in the bulk of the genome. Although repair elicited by pyrimidine dimers in alpha-DNA was the same as in the bulk DNA, that following treatment of cells with either aminomethyl trioxsalen or angelicin and near UV was markedly deficient in alpha-DNA. This deficiency reflected the removal of fewer adducts from alpha-DNA after the same initial adduct frequencies. These results could mean that each furocoumarin may produce several structurally distinct adducts to DNA in cells and that the capacity of cellular repair systems to remove these various adducts may vary greatly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Repair of furocoumarin adducts in mammalian cells. 653 Oct 19

Skin fibroblasts from normal human subjects were exposed in vitro to long-wave ultraviolet radiation (UVA, 320-400 nm) alone, or in combination with 8-methoxypsoralen (8-MOP). DNA damage was analysed with the alkaline elution technique before and after post-treatment incubation of the cells at 37 degrees C for various times. Cells treated with UVA at 1.1 J/cm/ showed an increased DNA elution rate, which returned to the normal level within 30 min of post-treatment incubation. In cells treated with PUVA (8-MOP at 20 microgram/ml plus UVA at 0.04 J/cm2), the alkaline elution rate was not different from untreated control cells, either before or after post-treatment incubation for time up to 7 days. When the PUVA treatment was followed first by a washing, to remove any unbound 8-MOP, and then by UVA (PUVA + UVA) at 1.1 J/cm2, the alkaline elution rate decreased below the control level. During the post-treatment incubation of the PUVA + UVA-treated cells there was a gradual increase of the alkaline elution rate to a level significantly above that in control cells. This increase was observed after 30 min. It reached a maximum after 24 h and remained after 7 days of post-treatment incubation. Cells from a patient with xeroderma pigmentosum of complementation group A, which were given the same PUVA + UVA treatment, did not show any change in the alkaline elution rate during the post-treatment incubation. If, as seems likely, an increased alkaline elution rate indicates as increase of DNA breaks, and a decreased alkaline elution rate indicates the sealing of breaks and/or the formation of cross-links, and results would suggest the following: (1) UVA irradiation in itself is capable of inducing DNA breaks, which are rapidly sealed during post-treatment incubation; (2) PUVA treatment induces mono-adducts, some of which appear to remain in the DNA for at least 7 days of post-treatment incubation and can be activated to form DNA cross-links by a second dose of UVA; (3) DNA cross-links induced by PUVA + UVA can be recognized by a repair process that involves the formation of DNA breaks. This process is not observed in xeroderma pigmentosum cells of group A.
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PMID:Induction and repair of psoralen cross-links in DNA of normal human and xeroderma pigmentosum fibroblasts. 706 32

Photoactivated 8-methoxypsoralen (8-MOP) has been proven to be clinically effective for a number of dermatological conditions including lichen planus, mycosis fungoides, and psoriasis. 8-MOP forms two types of covalent photoproducts with DNA, monoadducts, and bifunctional adducts which cross-link the two DNA strands. Angelicin is a congener of 8-MOP which forms only monoadducts. We have used the combined density and isotopic labeling technique to study repair replication in cultured human fibroblasts treated with either of these compounds and exposed to near-ultraviolet light. In human diploid fibroblasts (WI-38), the time course of repair replication for both compounds is similar. Drug concentration and ultraviolet 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). These results suggest that repair replication in response to 8-MOP is primarily a response to monoadducts and that the enzymatic pathway for this repair synthesis shares at least one step with the pathway for repair of pyrimidine dimers. Cross-link persistence in treated cells was assayed by use of 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.
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PMID:DNA repair in human cells containing photoadducts of 8-methoxypsoralen or angelicin. 747 Oct 88

Mitomycin C (MMC) induces various types of DNA damages that cause significant cytotoxicity to cells. Accordingly, repair of MMC-induced damages involves multiple repair pathways such as nucleotide excision repair, homologous recombination repair and translesion bypass repair pathways. Nonetheless, repair of the MMC-induced DNA damages in mammals have not been fully delineated. In this study, we investigated potential roles for Xeroderma pigmentosum (XP) proteins in the repair of MMC-induced DNA damages using an assay that detects the ssDNA patches generated following treatment with MMC or 8'-methoxy-psoralen (8-MOP) + UVA (ultraviolet light A). Human wild-type cells formed distinctive ssDNA foci following treatment with MMC or 8-MOP + UVA, but not with those inducing alkylation damage, oxidative damage or strand-break damage, suggesting that the foci represent ssDNA patches formed during the crosslink repair. In contrast to wild-type cells, mutant defective in XPE orXPG did not form the ssDNA foci following MMC treatment, while XPF mutant cells showed a significantly delayed response in forming the foci. A positive role for XPG in the repair of MMC-induced DNA damages was further supported by observations that cells treated with MMC induced a tight association of XPG with chromatin, and a targeted inhibition of XPG abolished MMC-induced ssDNA foci formation, rendering cells hypersensitive to MMC. Together, our results suggest that XPG along with XPE and XPF play unique role(s) in the repair of MMC-induced DNA damages.
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PMID:An in vivo analysis of MMC-induced DNA damage and its repair. 1625 76