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

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.
 ...
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.
 ...
PMID:DNA polymerases alpha beta and gamma in inherited diseases affecting DNA repair. 67 49

Fibroblasts from New Zealand Black mouse fetuses manifest increased frequency of chromosomal breaks and interchanges after exposure to ultraviolet radiation when compared with cells from BABL/c fetuses. This chromosomal instability is similar to what has been reported in cells from patients with xeroderma pigmentosum and may be related to the chromosomally abnormal clones and malignancy previously reported in adult New Zealand Black mice.
 ...
PMID:Ultraviolet radiation--induced chromosomal abnormalities in fetal fibroblasts from New Zealand black mice. 68 17

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.
 ...
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.
 ...
PMID:Excision of hydrocarbon-DNA adducts and consequent cell survival in normal and repair defective human cells. 69 69

Computed tomography (CT) scans in two young patients with xeroderma pigmentosum with neurologic manifestations (De Sanctis-Cacchione syndrome) showed ventricular dilatation and cerebral cortical atrophy. The brainstem appeared small. In addition, an abnormal thickening of the calvarial bones was noted in both patients. These CT findings of the brain were compared with the neuropathologic features of this syndrome reported in the literature.
 ...
PMID:Cranial computed tomography findings in xeroderma pigmentosum with neurologic manifestations (De Sanctis-Cacchione syndrome). 70 25

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.
 ...
PMID:Xeroderma pigmentosum: heterogeneous syndrome and model for UV carcinogenesis. 71 83

Biochemical and genetic information on xeroderma pigmentosum (XP) has been briefly reviewed. This indicates that 80 to 90 percent of all XP patients are defective in the excision repair of pyrimidine dimers and are unable to perform the first step of this process as shown, for example, by their inability to undergo the DNA superhelical changes which accompany the initiation of excision repair in normal cells. However, in spite of its apparent biochemical homogeneity, XP is genetically heterogeneous and many genes appear to be responsible for the function of the factor defective in XP. Ten to 20 percent of all XP patients (called XP-variants) are capable of "dimer excision repair" but have difficulties in replicating UV-damaged DNA. The defects of XP and XP-variant affect also the repair of DNA damage caused by a number of chemical mutagens and carcinogens. This has important theoretical and practical implications since it indicates, for example, that the repair systems defective in XP must have broad specificity and that even XP cells not exposed to the harmful effect of light may suffer from poor repair of DNA damage. With regard to cancer, two questions have been considered. Namely, does XP provide a valid general model for UV-carcinogenesis in man and does it show how DNA damage leads to malignant transformation? The first question was answered in the affirmative in view of some clinical but, mainly, of cell biological data indicating that normal and excision defective XP cells differ, more quantitatively than qualitatively, in their response to UV-light. With regard to the second question XP seems to provide some support for various theories on carcinogenesis and, DNA repair defects may favour actinic carcinogenesis in a complex, non-univocous manner. Possibly the most important lesson imparted by XP is that, in man, the stability of the genetic material is dependent on the function of repair systems whose failure may predispose to cancer. In addition, the study of XP has stressed the fact that many genes control DNA metabolism and new evidence is accumulating to show that defects in such genes may contribute significantly to the genetic predisposition to cancer.
 ...
PMID:Xeroderma pigmentosum and the role of DNA repair in oncogenesis. 71 84

Pigmented Xerodermoid is a variant of Xeroderma pigmentosum characterized by late manifestation of sun--sensitivity, dyschromic and poikilodermatic skin changes and multiple malignant skin tumors in light exposed areas. In contrast to Xeroderma pigmentosum excision repair system is normal, but DNA synthesis after UV--irradiation is markedly prolonged, suggesting that the postreplicational repair mechanism is disturbed. A family of 89 members with 4 siblings suffering from pigmented Xerodermoid was examined. The pedigree of this family suggests autosomal recessive inheritance in this disease.
 ...
PMID:Pigmented Xerodermoid: first report of a family. 71 86

Inhibition of HeLa cell DNA synthesis by DNA-damaging agents as a test for mutagenic carcinogens has been investigated further. Several mutagens and/or carcinogenic agents not previously assayed for DNA synthesis inhibition were tested and found to be positive. The effect of two DNA-damaging agents administered simultaneously was investigated: With ultraviolet light (UV) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) the effects were partly additive, whereas with MNNG and ICR-170 they were not. When UV was administered simultaneously with hydroxyurea (HU), a non-DNA-damaging inhibitor of DNA synthesis, the effects of the DNA-damaging agent were still evident after HU was removed and the HU-induced DNA synthesis inhibition reversed. Therefore, although the test probably cannot determine whethter there are one or more DNA-damaging agents in an unknown mixture, the presence of a powerful DNA synthesis inhibitor that is not a DNA-damaging agent will not mask the effects of a DNA-damaging agent in the same sample. Despite the fact that ICR-170 induces little DNA repair in xeroderma pigmentosum (XP) cells, which are deficient in excision repair, the inhibition of DNA synthesis induced by this agent was less in XP cells than in HeLa cells. The inhibition of DNA synthesis by MNNG was also less in XP than in HeLa cells. Therefore, contrary to expectations, the use of a repair-deficient cell did not increase the sensitivity of the test. Various in vitro mammalian cell tests are compared. Assays for unscheduled DNA synthesis are much less sensitive to intercalating agents, such as adriamycin, and to X-rays than are assays for inhibition of DNA synthesis but takes longer and requires more specialized skills than does measurement of DNA synthesis inhibition. Finally, the in vitro HeLa DNA synthesis inhibition test is compared with the in vivo DNA synthesis inhibition test with mouse testes.
 ...
PMID:DNA synthesis inhibition in HeLa cells as a simple test for agents that damage human DNA. 72 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>