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)

Caffeine is rapidly metabolized in human and mouse cells in culture by de-methylation: within 1-3 h of exposure to millimolar concentrations of labeled caffeine, more than 90% of the pool consists of labeled products of metabolism and less than 10% is still caffeine. The methyl groups seem to be transferred and used in the de novo synthesis of thymine, guanine, and adenine to nucleic acids. Normal fibroblasts, Lesch-Nyhan fibroblasts, xeroderma pigmentosum fibroblasts, HeLa cells, wild type mouse cells, and adenine phosphoribosyl-transferase-deficient mouse cells all seem to metabolize caffeine similarly.
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PMID:Metabolism of caffeine to nucleic acid precursors in mammalian cells. 95 Sep 53

Replicative bypass repair of UV damage to DNA was studied in a wide variety of human, mouse and hamster cells in culture. Survival curve analysis revealed that in established cell lines (mouse L, Chinese hamster V79, HeLa S3 and SV40-transformed xeroderma pigmentosum (XP)), post-UV caffeine treatment potentiated cell killing by reducing the extrapolation number and mean lethal UV fluence (Do). In the Do reduction as the result of random inactivation by caffeine of sensitive repair there were marked clonal differences among such cell lines, V79 being most sensitive to caffeine potentiation. However, other diploid cell lines (normal human, excision-defective XP and Syrian hamster) exhibited no obvious reduction in Do by caffeine. In parallel, alkaline sucrose sedimentation results showed that the conversion of initially smaller segments of DNA synthesized after irradiation with 10 J/m2 to high-molecular-weight DNA was inhibited by caffeine in transformed XP cells, but not in the diploid human cell lines. Exceptionally, diploid XP variants had a retarded ability of bypass repair which was drastically prevented by caffeine, so that caffeine enhanced the lethal effect of UV. Neutral CsC1 study on the bypass repair mechanism by use of bromodeoxyuridine for DNA synthesis on damaged template suggests that the pyrimidine dimerer acts as a block to replication and subsequently it is circumvented presumably by a new process involving replicative bypassing following strand displacement, rather than by gap-filling de novo. This mechanism worked similarly in normal and XP cells, whether or not caffeine was present, indicating that excision of dimer is not always necessary. However, replicative bypassing become defective in XP variant and transformed XP cells when caffeine was present. It appears, therefore, that the replicative bypass repair process is either caffeine resistant or sensitive, depending on the cell type used, but not necessarily on the excision repair capability.
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PMID:Replicative bypass repair of ultraviolet damage to DNA of mammalian cells: caffeine sensitive and caffeine resistant mechanisms. 96 89

Cells cultured from most patients suffering from the sunlight-sensitive hereditary disorder xeroderma pigmentosum are defective in the ability to excise ultraviolet light (UV)-induced pyrimidine dimers from their DNA. There is, however, one class of these patients whose cells are completely normal in this excision repair process. We have found that these cells have an abnormality in the manner in which DNA is synthesized after UV-irradiation. The time taken to convert initially low-molecular-weight DNA synthesized in UV-irradiated cells into high-molecular-weight DNA similar in size to that in untreated cells is much greater in these variants than in normal cells. Furthermore, this slow conversion of low to high-molecular-weight newly synthesized DNA is drastically inhibited by caffeine, which has no effect in normal cells. Two cell lines from classes of xeroderma pigmentosum that are defective in excision-repair show intermediate effects, with regard to both the time taken to convert newly synthesized DNA to high molecular weight and the inhibition of this process by caffeine.
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PMID:Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation. 105 97

We describe a reproducible technique for measuring DNA strand breaking and rejoining in cells after treatment with U.V.-light. Results obtained with normal human cells, xeroderma pigmentosum cells (XP, complementation group A) and XP variant cells suggest that all three of these cell-types can carry out single-strand incision with equal rapidity. However, the breaks so induced appeared to be only slowly rejoined in the XP variant cells and rejoined not at all in XP complementation group A cells. Furthermore, parental strand rejoining was inhibited by caffeine in XP variant cells but not in normal cells.
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PMID:DNA strand breaking and rejoining in response to ultraviolet light in normal human and xeroderma pigmentosum cells. 108 94

Some current controversies concerning the mechanism of postreplication repair in mammalian cells are discussed. We have found that two xeroderma pigmentosum cell lines normal in excision-repair are abnormal in postreplication repair. The rate of postreplication repair is slower than that in normal cells and is caffeine sensitive. In normal human fibroblasts, caffeine has little effect.
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PMID:Postreplication repair of DNA in UV-irradiated mammalian cells. 119 Nov 82

Compared to its effects on unirradiated cells, caffeine inhibited DNA chain elongation and joining in UV-irradiated xeroderma pigmentosum (XP) cells but not in irradiated normal human cells. The drug also inhibited the ability of XP cells to recover and make DNA of normal size at long times after irradiation.
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PMID:Effects of caffeine on postreplication repair in xeroderma pigmentosum cells. 119 Nov 84

Caffeine is shown to block repair of ultraviolet-irradiated adenovirus 2 when the irradiated virus infects normal human fibroblasts from a xeroderma pigmentosum (XP) variant. Such blockage is not observed when the irradiated virus infects XP fibroblasts belonging to XP complementation group A. Thus normal and XP variant cells have a caffeine-sensitive repair process. This may be either excision or an excision dependent repair process because fibroblasts belonging to XP complementation group A are believed to lack the excision repair process.
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PMID:Caffeine inhibition of the repair of ultraviolet-irradiated adenovirus in human cells. 121 24

A uniform response to UV of four normal cell strains was demonstrated. One excision-proficient xeroderma pigmentosum variant strain (XP7TA) had a wild-type UV response but a second (XP30RO) was more sensitive. An excision-deficient xeroderma pigmentosum strain XP4L0 was substantially more sensitive than wild-type cell strains. A continuous post-irradiation treatment with non-toxic levels of caffeine enhanced the lethal effect of UV light in both xeroderma pigmentosum variant cell strains but not in cells from normal individuals. There was no detectable effect on cells from a xeroderma pigmentosum individual from complementation group A. These results correlate well with observations on the influence of caffeine on post-replication repair in the three classes of cells.
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PMID:The influence of caffeine on cell survival in excision-proficient and excision-deficient xeroderma pigmentosum and normal human cell strains following ultraviolet-light irradiation. 121 25

A 65-year-old Japanese man with a xeroderma pigmentosum (XP) variant, XP127TO, is described. The XP127TO skin fibroblasts exhibited the typical XP variant characteristics of a 1.5-fold higher sensitivity than normal cells to the lethal effect of 254 nm ultraviolet (UV) light and the normal level of unscheduled DNA synthesis induced by 254 nm UV. Caffeine dose-dependently increased the cytotoxic effect of 254 nm UV on XP127TO cells. Clinically, the patient developed not only 3 cutaneous squamous cell carcinomas on sun-exposed areas but also an adenocarcinoma of the upper lobe of the right lung. A review of the 14 documented Japanese XP patients with nonskin malignancies indicates that the incidence of nonskin malignancy in XP patients is much lower than that of skin cancer in XP but higher than that in the general population.
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PMID:Xeroderma pigmentosum variant associated with multiple skin cancers and a lung cancer. 139 8

Ultraviolet radiation (UV) in sunlight induces an abnormally high incidence of skin cancer in patients with xeroderma pigmentosum (XP), an autosomal recessive disease with defects in the repair of damaged DNA. We determined the frequency of UV-induced chromosomal aberrations in cultured lymphoblast lines from a patient with the variant form of XP, from a patient with the complementation group E form, and from two patients with the complementation group C form. In contrast to results with patients having other forms of XP, the group E and variant patients showed no abnormal increase in UV-induced chromosomal aberrations. Even in the presence of caffeine, which exacerbates the postreplication repair defect of UV-irradiated XP variant cells, there was still no abnormally elevated frequency of UV-induced chromosomal aberrations in the variant cells. These results, indicating that the level of UV-induced chromosomal aberrations is not correlated with these patients' marked susceptibility to skin cancer, suggests that some mechanism other than genetic transposition is causatively related to these XP patients' high incidence of sunlight-induced skin cancer.
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PMID:Skin cancer and chromosomal aberrations induced by ultraviolet radiation. Evidence for lack of correlation in xeroderma pigmentosum variant and group E patients. 160 53


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