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 influence of caffeine on cytotoxicity and postreplication repair of DNA was examined following exposure of several cell types to physical and chemical agents known to damage DNA. The cell types used in this study were normal human fibroblasts (HS-WP), human xeroderma pigmentosum fibroblasts (SGL), Chinese hamster V79 cells, mouse BALB/c-3T3 cells, and secondary Syrian hamster embryo cells. The DNA damaging agents were ultraviolet light (UV), N-2-acetoxy-fluorenylacetamide (AFAA), nitroquinoline-N-oxide (NQO) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Induction of cytotoxicity in Chinese hamster V79 cells due to ultraviolet light or AFAA exposure was enhanced by caffeine at a concentration of 1.0 mM in the culture medium, but not at 0.2 or 0.05 mM. Caffeine also inhibited postreplication repair in these cells at the same concentrations. In contrast, postreplication repair was not affected by caffeine at concentrations up to 1.0 mM in normal human fibroblasts (HS-WP), human xeroderma pigmentosum fibroblasts (SGL), secondary Syrian hamster embryo cells, and mouse BALB/c-3T3 cells following treatment with ultraviolet light, AFAA, NQO, or MNNG. Cytotoxicity in BALB/c-3T3 cells following exposure to ultraviolet light or AFAA was enhanced in the presence of caffeine at 1.0 or 0.2 mM, although these concentrations of caffeine had no effect on postreplication repair in these cells. The inhibitory effect of caffeine on postreplication repair was found only in Chinese hamster V79 cells among the five cell types used in this study. Both normal and xeroderma pigmentosum human cells repaired mutagen-induced DNA damage equally well in the absence or presence of caffeine at concentrations of 1.0 mM or less.
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PMID:Variations among species and cell types in the effects of caffeine on mutagen-induced cytotoxicity and postreplication repair of DNA. 680 26

Sister-chromatid exchange (SCE) induced by ultraviolet (UV) irradiation and viability after UV irradiation were studied in lymphoblastoid cell lines derived from 7 patients with xeroderma pigmentosum (XP) and 6 normal donors. UV irradiation caused significant increases of SCEs in both XP and normal cells. In 3 XP cell lines, which were deficient in unscheduled DNA synthesis (UDS) and sensitive to the killing effect of UV, very high SCE frequencies were observed after UV irradiation. Cells from a patient with the De Sanctis-Cacchione syndrome were the most sensitive to UV in terms of both SCE induction and cell killing. In 2 of 4 UDS-proficient XP cell lines tested, the incidences of UV-induced SCEs were similar to those in normal cell lines, but in 2 other UDS-proficient lines from 2 XP patients with skin cancer, the frequencies of UV-induced SCEs were significantly higher than in normal cells. Continuous post-UV treatment with 1 mM caffeine markedly enhanced UV-induced SCEs in 3 of 4 UDS-proficient XP cell lines but had only slight effects on cells from the 4th UDS-proficient XP patient and from normal individuals.
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PMID:Differential features of sister-chromatid exchange responses to ultraviolet radiation and caffeine in xeroderma pigmentosum lymphoblastoid cell lines. 686 88

Effects of elastatinal, a protease inhibitor, on DNA repair and its cytotoxicity were investigated in normal human, xeroderma pigmentosum and Chinese hamster V79 cells. There were no effects of elastatinal on DNA repair and UV-induced sister chromatid exchanges, and all 3 cell lines demonstrated essentially the same sensitivity to the cytotoxic effect of elastatinal. These results were quite different from those by antipain, another protease inhibitor, and caffeine.
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PMID:Cytotoxic effects of protease inhibitors on human cells. 2. Effect of elastatinal. 719 73

Human cells irradiated with UV light synthesize lower molecular weight DNA than unirradiated cells. This reduction in molecular weight is greater in xeroderma pigmentosum (XP) cells than in normal cells. The molecular weight of DNA is further reduced by the addition of caffeine to XP cells. By several hours after irradiation, DNA fragments are barely detectable. Cells from excision-proficient and excision-deficient XP patients were studied autoradiographically to produce cytological evidence of DNA chain elongation. Replicate cultures with and without caffeine were synchronized and irradiated with UV light during the S phase. Caffeine was removed in G2, and the cells were labeled with 3H-thymidine. Results showed significantly increased labeling during G2 of excision-deficient XP cells. Labeling was dependent on the time of irradiation and presence of caffeine. The XP variant cells had no increase in labeling for any irradiation time.
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PMID:Cytological evidence for DNA chain elongation after UV irradiation in the S phase. 724 30

Clinical and photobiological differences between Japanese patients belonging to xeroderma pigmentosum (XP) variant and complementation group A were studied, especially focussing on XP variants. All of the XP variant patients commonly manifested a delayed onset of pigmented freckles as the initial symptom around 5--7 years old without acute sun erythema, in contrast to the early manifestation of acute solar erythema during infancy in XP group A patients. Six XP variant patients tested showed normal and three showed low minimal erythema doses (MEDs), at the 24 h reaction peak after monochromatic u.v. (280--330 nm) irradiation, while XP group A patients had definitely low MEDs (280--350 nm) with abnormally delayed peaking of the erythema reaction at 72 h. In cell culture studies, all XP variant strains exhibited normal levels of 254 nm u.v.-induced, unscheduled DNA synthesis (UDS), 1.4--2 times more accumulation of excision DNA breaks by arabinofuranosyl cytosine and hydroxyurea due to a subtle defect in the later polymerization step of excision repair, and a slightly higher sensitivity to u.v. cell killing than did normal cells. With respect to the synergistic effect of caffeine on u.v. lethality, XP variant strains could be divided into caffeine-susceptible (eight cases) and caffeine-resistant (two cases) subgroups. The extent of excision-break accumulation was greater in the former subgroup than in the latter. All of eight XP variant patients whose cells showed caffeine potentiation of u.v. lethality had already had skin malignancies, but two sib patients whose cells were caffeine-resistant had as yet had no neoplasm. It is strongly suggested that in XP variant, caffeine-susceptibility may be related to the development of neoplasms.
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PMID:Clinical and photobiological characteristics of Japanese xeroderma pigmentosum variant. 725 73

Caffeine, hexamidine, Lm8, methionine, ATP, ionol, and vitamin E enhance the proliferation of the normal embryonic culture of human fibroblasts. Arginine, streptomycin and cysteamine exert no action on the growth of the culture. Analysis of similar effects on the culture of xeroderma pigmentosum has demonstrated that caffeine, hexamidine, Lm3 and vitamin E also enhance the proliferation of the culture. Ionol produces no effect on the culture of xeroderma pigmentosum. The mutagenic agent dioxidine causes a sharp inhibition of the proliferation of normal embryonic culture and has no effect on the culture of xeroderma pigmentosum
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PMID:[Antimutagenic properties of a series of drug compounds]. 728 8

As shown previously, newly synthesized DNA from Chinese hamster, excision proficient and excision deficient xeroderma pigmentosum (XP) cells treated with split doses of N-acetoxy-acetylaminofluorene (AAAF) or ultraviolet radiation (uv) is larger in size than DNA from cells treated with only the single dose. In this report we determined the effects of caffeine, an inhibitor of postreplication repair, upon enhancement of repair by a split dose treatment with AAAF. Caffeine was added to cells either immediately following the first or the second dose of AAAF and the size of newly synthesized DNA was determined by alkaline sucrose gradient sedimentation. Results showed that: (a) the DNA from V79 and XP cells incubated with caffeine between the first and second dose of AAAF was smaller in size than DNA from cells not incubated with caffeine; (b) caffeine exhibited a lesser effect when added after the second dose during the pulse-chase; and (c) caffeine has little effect upon daughter DNA of normal human cells treated with single or split doses of AAAF. These data indicate that caffeine interferes with the enhancement of postreplication repair in V79 and XP cells treated with AAAF.
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PMID:Modulation by caffeine of enhanced postreplication repair in mammalian cells treated with N-acetoxy-acetylaminofluorene. 744 Nov 10

We have studied the effect of caffeine on gene- and strand-specific DNA repair after exposure of Chinese hamster ovary cells and human xeroderma pigmentosum complementation group C (XPC) cells to ultraviolet irradiation (UV). In hamster cells, caffeine inhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolate reductase (DHFR) gene by up to 66% after 8 h of repair incubation. This effect was dose-dependent, with more inhibition at 10 than at 1.5 mM caffeine. The inhibition was due to decreased repair in the transcribed strand of the hamster DHFR gene. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of UV-induced cell killing by caffeine. DNA repair was also measured in the overall genome by repair-replication analysis. In hamster cells, caffeine caused a modest enhancement of repair. Caffeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in early S phase during the 24 h post-irradiation period. In XPC cells, 10 mM caffeine inhibited the removal of CPDs from the transcribed strand of the DHFR gene by 92%. The removal of all photoproducts from the overall genome was inhibited by 26% in these cells. Since the residual repair in XPC cells is thought to occur in active genomic regions, we propose that caffeine preferentially inhibits gene-specific repair.
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PMID:Caffeine inhibits gene-specific repair of UV-induced DNA damage in hamster cells and in human xeroderma pigmentosum group C cells. 776 78

Six Japanese patients in Hokkaido area were diagnosed as xeroderma pigmentosum (XP) at two University Hospital; one patient, a 29 years old female (XP2AS) at Asahikawa Medical College, and five patients, namely, a 53 years old male (XP1SA), a 45 years old female (XP2SA), a 46 years old female (XP3SA), a 47 years old male (XP4SA) and a 34 years old male (XP5SA) at Hokkaido University School of Medicine. All these XP patients showed mild skin symptoms and had no apparent neurological abnormalities. To identify genetic complementation groups of these patients, DNA repair capacities in skin fibroblasts derived from the patients were analyzed by ultraviolet light (UV)-induced unscheduled DNA synthesis (UDS), and also by colony-forming abilities of UV-irradiated cells incubated with or without caffeine added in post-UV culture medium. The levels of UDS measured by autoradiography in these XP cells irradiated with 20 J/m2 of UV were 67 to 84% of those of normal human fibroblasts. Although one XP cell strain (XP2AS) showed about 2-fold greater sensitivity to killing by UV than normal cells, UV sensitivities of the rest of 5 XP strains were similar or only slightly higher than those of normal cells. However, UV sensitivities of all the 6 XP cell strains markedly increased by addition of 1 mM caffeine in the post-UV incubation medium, a phenomenon characteristic of XP variant cells. We also analyzed post-replication repair in XP1SA cells by sedimentation of newly-synthesized DNA in alkaline sucrose gradient, and found that this strain is defective in this repair system. From these results, we concluded that all the 6 XP strains studied here belong to XP variants.
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PMID:Assignment of six patients with xeroderma pigmentosum in Hokkaido area to a variant form. 783 Feb 60

The neurodegeneration and amyloid deposition of sporadic Alzheimer disease (AD) also occur in familial AD and in all trisomy-21 Down syndrome (DS) patients, suggesting a common pathogenetic mechanism. We investigated whether defective processing of damaged DNA might be that mechanism, as postulated for the neurodegeneration in xeroderma pigmentosum, a disease with defective repair not only of UV radiation-induced, but also of some oxygen free radical-induced, DNA lesions. We irradiated AD and DS skin fibroblasts or blood lymphocytes with fluorescent light, which is known to cause free radical-induced DNA damage. The cells were then treated with either beta-cytosine arabinoside (araC) or caffeine, and chromatid breaks were quantified. At least 28 of 31 normal donors and 10 of 11 donors with nonamyloid neurodegenerations gave normal test results. All 12 DS, 11 sporadic AD, and 16 familial AD patients tested had abnormal araC and caffeine tests, as did XP-A cells. In one of our four AD families, an abnormal caffeine test was found in all 10 afflicted individuals (including 3 asymptomatic when their skin biopsies were obtained) and in 8 of 11 offspring at a 50% risk for AD. Our tests could prove useful in predicting inheritance of familial AD and in supporting, or rendering unlikely, the diagnosis of sporadic AD in patients suspected of having the disease.
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PMID:Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture. 864 43


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