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)

Uracil DNA N-glycosidase, an enzyme which participates in the excision of uracil from DNA, was measured in extracts from fibroblasts lines cultured from normal subjects, from several subjects with the genetic disease xeroderma pigmentosum, and from a subject with ataxia telangiectasia. The cell lines representative of complementation groups A and D of xeroderma pigmentosum and of ataxia telangiectasia had roughly the same level of activity as did the normal cells. On the other hand, cells from two xeroderma pigmentosum variants (XP4BE and XP13BE) had roughly half the normal level of activity, and cells from the heterozygous mother of XP4BE had an intermediate level of activity. In spite of these quantitative differences, no systematic alterations in reaction characteristics, apparent Km for substrate, or purification characteristics were noted for enzyme from any of the lines. Thus a causal relationship, if any, between levels of activity and the disease symptoms is equivocal.
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PMID:Human uracil DNA N-glycosidase: studies in normal and repair defective cultured fibroblasts. 64 2

Exposure of cultured human fibroblasts to hyperthermia delayed the host-cell reactivation of UV-irradiated human adenovirus type 12 (AD12). The experimental design consisted of irradiating human AD12 with UV doses ranging from 180 to 1800 ergs/mm2, infecting human cell populations at 37 degrees C, exposing the infected cells for 7 h to 39.5 degrees C and 41.8 degrees C, returning them to 37 degrees C and estimating the frequency of cells with intranuclear viral inclusion bodies (IB) 41 and 89 h after hyperthermia treatment. Hyperthermia reduced the fractions of fibroblasts with viral IB in the 41 h samples. By 89 h the capacity to form IB in the treated cells was comparable to that in control cells. Hyperthermia of 39.5 and 41.8 degrees C for 7 h did not affect the replication of nonirradiated AD12. The pattern of host-cell reactivation of AD12 following hyperthermia was compared to that in DNA repair deficient xeroderma pigmentosum cell populations.
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PMID:Hyperthermia and host-cell reactivation of adenovirus 12. 65 3

The repair of human DNA after damage by known and potential metabolites of benzo(a)pyrene has been examined utilizing the bromodeoxyuridine photolysis assay. Repair was characterized as either ultraviolet ("long") or ionizing radiation type ("short") repair utilizing normal cells and cells deficient in ultraviolet-type repair endonuclease from a patient with xeroderma pigmentosum (XP). We have found that only (+/-)-7beta,8alpha-dihydroxy-9beta,-10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BP diol epoxide 1) and its disastereomer, (+/-)-7beta,8alpha,-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BP diol epoxide 2) elicit damage to DNA which is recognizable by the ultraviolet excision repair system in normal human cells. Benzo(a)pyrene 4,5-, 9,10-, 11,12-oxides do not elicit damage which is repairable by this repair system. The 1,2-diol-3,4-epoxides from naphthalene have no measurable activity in our assay. These results indicate that both the benzo(a)pyrene ring structure and the diol epoxide groups are important in causing the damage to DNA which is repairable by the ultraviolet excision repair system. These results parallel the reported high mutagenic activity of these compounds and support the concept that benzo(a)pyrene 7,8-diol-9,10-epoxides may be the ultimate, metabolically activated forms of benzo(a)pyrene.
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PMID:Repair of DNA damaged by mutagenic metabolites of benzo(a)pyrene in human cells. 65 91

We have examined the ability of normal fibroblasts and of excision-deficient xeroderma pigmentosum (XP) and XP variant fibroblasts to perform postreplication DNA repair after increasing doses of either ultraviolet (UV) irradiation or mutagenic benzo(a)pyrene derivatives. XP cells defective in the excision of both UV-induced pyrimidine dimers and guanine adducts induced by treatment with the 7,8-diol-9,10-epoxides of benzo(a)pyrene were partially defective in their ability to synthesize high molecular weight DNA after the induction of both classes of DNA lesions. This defect was more marked in XP variant cells, despite their ability to remove by excision repair both pyrimidine dimers and the diol epoxide-induced lesions to the same degree as observed in normal cells. The benzo(a)pyrene 9,10-oxide had no effect in any of the 3 cell lines. The response of the excision and postreplication DNA repair mechanisms operating in human fibroblasts treated with benzo(a)pyrene 7,8-diol-9,10-epoxides, therefore, appears to resemble closely that seen after the induction of pyrimidine dimers by UV irradiation.
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PMID:Postreplication repair of DNA in human fibroblasts after UV irradiation or treatment with metabolites of benzo(a)pyrene. 65 92

Benzo(a)pyrene diol-epoxide I (r-7,t-8,dihydroxy-t-9,10 oxy-7,8,9,10 tetrahydrobenzo(a)pyrene) was used to treat either human adenovirus 5 or cultures of human fibroblasts. The survival of diol-epoxide I treated adenovirus was greater when infecting fibroblasts from normal persons than when infecting fibroblasts from patients with xeroderma pigmentosum (XP). One diol-epoxide I molecule bound per viral genome correlated with one lethal hit as measured using XP fibroblasts. Normal fibroblasts blocked in semi-conservative DNA synthesis incorporated into their DNA more [3H]thymidine in response to diol-epoxide I treatment than did XP fibroblasts, and also excised more diol-epoxide I from their DNA. All of the effects described above were similar to those obtained when the inactivating agent was ultraviolet light rather than benzo(a)pyrene diol-epoxide I.
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PMID:Excision repair by human fibroblasts of DNA damaged by r-7, t-8-dihyroxy-t-9,10-oxy-7,8,9,10- tetrahydrobenzo(a)pyrene. 67 21

We have studied the response of human cells in culture to cis platinum[II] diammine dichloride (cis Pt[II]) induced DNA damage. The survival data, measured as a function of cis Pt[II] dose were similar in a normal cell line (Human foetal lung) compared to a UV-sensitive, thymine dimer excision repair-deficient cell line (Xeroderma pigmentosum). However, there was a marked difference between the two cell lines when binding to DNA was plotted against dose of cis Pt[II] given for 1 h. When these findings were expressed as cell survival versus binding to DNA, a 4.1--fold difference between the slopes of the survival curves for the two cell lines was obtained. These findings are consistent with the notion that normal cells are able to excise cis Pt[II] induced damage from their genome and thus increase their ability to survive as compared to excision-deficient cells. An endonuclease preparation from Micrococcus luteus is able to recognise UV damage in DNA, but did not recognise cis Pt[II] induced damage. These results possibly indicate differences in the pathways of repair of damage caused by the two agents.
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PMID:Increased sensitivity of UV-repair-deficient human cells to DNA bound platinum products which unlike thymine dimers are not recognized by an endonuclease extracted from Micrococcus luteus. 67 24

Fibroblasts derived from patients with diseases affecting DNA repair processes, such as Xeroderma Pigmentosum (classical and variant), Fanconi's anemia, Bloom's syndrome, Ataxia Telangiectasica, Progeria and Werner's syndrome, were assayed for the three DNA polymerases. The specific activities of these enzymes were found within the limits observed in normal human fibroblasts. Also the sedimentation properties of the three polymerases were unaltered.
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PMID:DNA polymerases alpha beta and gamma in inherited diseases affecting DNA repair. 67 49

Fetal autopsy case of xeroderma pigmentosum was reported. This male fetus of 24 gestational weeks was prenatally diagnosed as xeroderma pigmentosum by detecting the DNA-repair defect of the amniotic fluid cells. Autopsy revealed not only maldevelopment of the fetus (stillbirth) in general for the standard, but also showed slight developmental retardation of various organs including kidneys and lungs, which could be examined by microscopic analysis. It was suggested that abnormality of the somatic organs began to appear at the fetal stage in this case of xeroderma pigmentosum.
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PMID:Fetal case of xeroderma pigmentosum--first report of an autopsy case. 68 92

Survival curves for normal human cells and xeroderma pigmentosum variant cells (XP4BE) after ultraviolet radiation were indistinguishable. In comparison, cells from xeroderma pigmentosum complementation group A (XP12BE) were very sensitive to ultraviolet radiation. Complementation group C (XP2BE) cells were almost as sensitive as group A cells. These survival phenomena parallel to known unscheduled DNA synthesis responses of these cells to ultraviolet radiation, which, compared with normal cells, are: XP4BE, 100%; XP2BE, 20%; XP12BE, 2%. The relative capacities of these cells to excise 7-bromomethylbenz[a]anthracene-DNA adducts and to survive treatment with the carcinogen were similar to the responses to ultraviolet irradiation, except that the XP2BE cell line both excised and survived this damage far better than anticipated from its response to ultraviolet irradiation. Moreover, whilst in the normal cells and variant cells the ratio of hydrocarbon-adenine adduct to hydrocarbon-guanine adduct remaining in DNA decreased notably with excision, this ratio did not change significantly with excision in the XP2BE cell line. The relationship between greater excision capacity and increased cell survival in the experiments with the chemical carcinogen indicates that the unexcised damage is responsible for the cell-killing action of this agent. The different relative repair and survival responses of these cell lines to ultraviolet irradiation on the one hand, and to 7-bromomethylbenz[a]anthracene chemical carcinogen treatment on the other, indicate that in at least one of these cell lines (XP2BE), and possibly in all the lines, different cellular mechanisms are involved in the repair of DNA damage resulting from ultraviolet irradiation and that resulting from the chemical carcinogen treatment.
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PMID:Excision of hydrocarbon-DNA adducts and consequent cell survival in normal and repair defective human cells. 69 69

Xeroderma pigmentosum (XP) is a rare inherited, heterogeneous syndrome with pigment anomalies, sun sensitivity, multiple cutaneous neoplasms and abnormal self protecting systems (SPS). The transmittence is autosomal-recessive. 50 percent of XP patients gets melanoma and 15 percent have neurological abnormalities. Clinical differentiation, determination of the DNA repair rate and cell fusion studies allow the differentiation of 6 complementation groups including De Sanctis-Cacchione syndrome and the XP variant typ. Pigmented Xerodermoid is a special form. Cytogenetic studies give evidences for the model character of XP for UV carcinogenesis.
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PMID:Xeroderma pigmentosum: heterogeneous syndrome and model for UV carcinogenesis. 71 83


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