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)

The survival of excision-deficient and of excision-proficient (variant) skin fibroblasts from xeroderma pigmentosum (XP) donors was about 5 times and twice, respectively, more sensitive to formaldehyde (FA) treatment than that of skin fibroblasts from healthy and XP heterozygote donors. The capacity of FA-treated host cells to further support Herpes virus (HSV) replication was also more sensitive to FA in XP12BE (group A) than in normal (KD) cells. An important recovery of this capacity occurred in both cell types when they were infected at increasing times (up to 36 h) after FA treatment. This contrasts with the decreasing capacity observed in XP12BE when similarly infected at increasing times after exposure to ultraviolet. In addition, the survival of FA-treated HSV was comparable in KD and XP12BE cells, whereas that of UV-irradiated HSV was much lower in XP12BE than in KD cells.
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PMID:Survival and herpes virus production of normal and xeroderma pigmentosum fibroblasts after treatment with formaldehyde. 22 86

Xeroderma pigmentosum (XP) is a hereditary disease characterized by a defect in the excision-repair mode of ultraviolet light damage and a high incidence of skin tumors. Cultured fibroblasts from normal and XP cells at low population doubling times were compared by induction of mild spreading of their nuclear constituents in a highly alkaline solution containing detergent and formaldehyde. In each XP culture a certain fraction (10-80%) of the nuclei were abnormal (50-80% in cell lines from children with XP-C disorders and 10-35% from embryonic and adult XP cells). Although their chromatin threads appeared normal in structure, they were separated by intervals up to 5 times the normal spacing. In all XP cells having this abnormal spacing in the chromatin, fibrils of nucleolar origin were approximately doubled in thickness, denser and less tufted, and nucleolar granules were few and dispersed. We suggest that this study reveals an abnormal weakness of the chromatin in some XP cells which results in the breakage of some DNA fibers in our preparative alkaline conditions. This weakness may be related to single-stranded breaks induced by metabolism of a high level of active oxygen species. These nuclear changes in XP cells are similar to those which have been associated with normal or pathologic senescence.
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PMID:Chromatin and nucleolar changes in Xeroderma pigmentosum cells resemble aging-related nuclear events. 291 Dec 72

The alkaline elution technique was used to study repair of DNA damage caused by formaldehyde (HCHO) in human bronchial epithelial cells and fibroblasts, skin fibroblasts, and DNA excision repair-deficient skin fibroblasts from donors with xeroderma pigmentosum. Exposure of cells to HCHO resulted in DNA-protein cross-links (DPC) and DNA single-strand breaks (SSB) in all cell types. DPC were induced at similar levels and were also removed by all cell types, with a half removal time of 2 to 3 hr. HCHO caused more SSB in the normal cell types than in the xeroderma pigmentosum fibroblasts. However, in all cell types, including the xeroderma pigmentosum cells, HCHO-induced DNA SSB and DPC were removed at comparable rates. By excision repair of HCHO-induced DNA damage, normal cells generated SSB that were also readily repaired. HCHO was only moderately cytotoxic to normal bronchial epithelial cells and fibroblasts at concentrations that induced substantial DNA damage. HCHO enhanced the cytotoxicity of both ionizing radiation and N-methyl-N-nitrosourea in both cell types. The results indicate that most DPC caused by HCHO can be removed without the involvement of DNA excision repair. Furthermore, HCHO also directly causes DNA SSB as well as SSB generated indirectly during ultraviolet-type excision repair. These studies indicate the complexity of the HCHO-induced DNA damage and its repair and that HCHO may enhance the cytotoxicity of chemical and physical carcinogens in human cells.
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PMID:Repair of DNA damage caused by formaldehyde in human cells. 646 94

In this investigation, the combination of 1-beta-D-arabinofuranosylcytosine and hydroxyurea was used to inhibit the polymerase step of DNA excision repair. The DNA single-strand breaks (SSB), which accumulated in the presence of these agents, were measured by alkaline elution. With this approach, DNA SSB were detected in normal human fibroblasts after exposure to trans-platinum(II)diamminedichloride, formaldehyde, or potassium chromate. These agents all share the common feature that they induce DNA-protein cross-links in mammalian cells. In the case of trans-platinum(II)diamminedichloride or formaldehyde, the frequency of these SSB was markedly less in excision-deficient xeroderma pigmentosum cells. With chromate, a high level of SSB was induced in both normal and xeroderma pigmentosum cells; these results indicate that chromate damage to DNA is repaired by a mechanism different than the classical excision pathway since xeroderma pigmentosum cells responded normally. Several other agents were investigated with this approach, and no SSB were detected with nickel sulfate, 12-O-tetradecanoylphorbol-13-acetate or asbestos fibers in the presence of the polymerase inhibitor. This approach was found to be a very sensitive method to detect DNA excision repair.
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PMID:Detection of DNA single-strand breaks produced during the repair of damage by DNA-protein cross-linking agents. 719 6

We have previously shown that the alkaline Comet assay (single cell gel electrophoresis) in a modified version is a sensitive test for the detection of formaldehyde-induced DNA-protein crosslinks (DPC). Our results also indicated that formaldehyde-induced DPC are related to the formation of chromosomal effects such as micronuclei and sister chromatid exchanges. To better understand the genetic consequences of formaldehyde-induced DPC we have now investigated the induction and removal of DPC in relationship to the formation of micronuclei in normal and repair-deficient human cell lines. We did not find significant differences between normal cells, a xeroderma pigmentosum (XP) cell line and a Fanconi anaemia (FA) cell line with respect to the induction and removal of DPC. However, the induction of micronuclei was enhanced in both repair-deficient cell lines, particularly in XP cells, under the same treatment conditions. Comparative investigations with the DNA-DNA crosslinker mitomycin C (MMC) revealed a delayed removal of crosslinks and enhanced induction of micronuclei in both repair-deficient cell lines. FA cells were found to be particularly hypersensitive to micronucleus induction by MMC. In contrast to the results with formaldehyde, induction of micronuclei by MMC occurred at much lower concentrations than the effects in the Comet assay. Our results suggest that more than one repair pathway can be involved in the repair of crosslinks and that disturbed excision repair has more severe consequences with regard to the formation of chromosomal aberrations after formaldehyde treatment than has disturbed crosslink repair.
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PMID:Induction and repair of formaldehyde-induced DNA-protein crosslinks in repair-deficient human cell lines. 1064 May 35