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)

Fifty xeroderma pigmentosum patients in Japan were examined for clinical characteristics and DNA repair of their cells, Skin cancers developed in 22 patients. Most of the patients without skin cancers were children, except for 5 older patients who had intermediate or nearly normal levels of DNA repair in their cells. All patients younger than 10 years old had no or very low activity of unscheduled DNA synthesis after ultraviolet light irradiation. Three genetic complementation groups, A, D, and E, and variants were found. Many Group A patients and no Group C patients characterized Japanese patients, compared with those in Europe and the United States, where Group C patients were most frequent. The high frequency of patients with low DNA repair capacities in their cells may account for the apparent high frequency of xeroderma pigmentosum patients in Japan. Age distribution of the cancer-bearing patients and their DNA repair characteristics suggest that almost all xeroderma pigmentosum patients will develop skin cancers unless their cells have nearly normal levels of DNA repair.
Cancer Res 1977 Feb
PMID:DNA repair characteristics and skin cancers of xeroderma pigmentosum patients in Japan. 83 73

Postreplication repair of DNA damage after ultraviolet light irradiation has been examined in a wide variety of human fibroblast strains. The donors were patients with xeroderma pigmentosum (XP) of different complementation groups or other hereditary disorders with indications of radiosensitivity, or with light sensitivity or multiple cancers. The defect in postreplication repair previously found in XP variants (excision-proficient XP's) has now been observed in a total of five XP variants and a less severe defect in postreplication repair has been found in excision-defective XP's in Complementation Groups A, B, C, and D. Complementation Group E and all other cell strains studied showed a response that was not significantly different from that of cells from normal donors. Excision repair was also measured in some of these cell strains and was found to be defective only in XP cells. Ultraviolet cell survival characteristics have been obtained for may of the cell strains. The most sensitive were cells from the excision-deficient XP's and from a sun-sensitive child (11961); the latter had no measurable defect in either excision or postreplication repair. The rest of the survival curves lay in a band limited by normal cell strains on the one hand and the slightly more sensitive excision-proficient XP variant XP30RO. Only in the case of the variants XP30RO and XP7TA were we able to demonstrate any influence of caffeine on cell survival.
Cancer Res 1977 Mar
PMID:Repair of ultraviolet light damage in a variety of human fibroblast cell strains. 83 85

An assay has been developed to measure the ability of human lymphocytes to repair damage to DNA. In this assay, purified human lymphocytes are exposed to graded doses of radiation and then stimulated with phytohemagglutinin to undergo DNA replication. The rate of incorporation of thymidine in irradiated lymphocytes during the second and subsequent rounds of DNA replication is taken to be indicative of the ability of the cells to repair damage to DNA. In lymphocytes from normal individuals, X-irradiation with doses of 100 to 800 rads was found to inhibit phytohemagglutinin-stimulated thymidine incorporation proportionally to the dose of radiation without curtailing the induction of DNA polymerase. The response to phytohemagglutinin of lymphocytes from a patient with xeroderma pigmentosum after exposure to graded doses of X-irradiation was found to be similar to that of the normal controls, whereas the response after ultraviolet irradiation was markedly impaired. In contrast, lymphocytes from patients with ataxia telangiectasia were hypersensitive to X-irradiation. The data on these clinical syndromes support the idea that this assay measures DNA repair and indicates the feasibility of using this method for screening individuals for genetic deficits in DNA repair.
Cancer Res 1977 Oct
PMID:Screening for deficits in DNA repair by the response of irradiated human lymphocytes to phytohemagglutinin. 90 9

The effect of exposure to UV irradiation or to the N-acetoxy-ester derivatives of four carcinogenic aromatic amides, 4-acetylaminobiphenyl (AABP), 2-acetylaminofluorene (AAF), 2-acetylaminophenanthrene, and 4-acetylaminostilbene, on cell survival was compared in strains of cultured human fibroblasts possessing normal rates of excision repair of DNA and in three strains of xeroderma pigmentosum (XP) cells, each differing in its rate of excision repair. The survival of each strain after exposure to UV reflected its capacity to repair DNA. Thus the slope of the survival curve for the XP strain with the poorest capacity for excision repair (XP12BE complementation group A) was 5.8-fold steeper than the exponential portion of the curve for the normally repairing strains; that of XP2BE (complementation group C) was 1.95-fold; and that of XP4BE (a variant capable of a normal rate of dimer excision) was only 1.3-fold steeper. The slope of the survival curves after exposure to each N-acetoxy ester derivative for these same XP strains averaged 6.4, 2.0, and 1.4 times steeper, respectively, than that of the normal strains tested. The excision repair capacity of these lines after exposure to N-acetoxy-AAF (50 muM/ml) was tested with alkaline cesium chloride density gradient centrifugation to detect incorporation of tritiated thymidine into nonreplicated DNA. The normal strains and XP4BE exhibited DNA excision repair by this method, whereas XP patients 2 and 12 did not. The cytotoxic effect of the four parent aromatic amide carcinogens, their N-hydroxy derivatives, as well as the N-acetoxy ester of each of the four N-hydroxy compounds and the N-sulfate ester of N-hydroxy-AAF and N-hydroxy-AABP in the XP2BE strain, was compared with their effect on the normal fibroblasts. The parent amides proved to be noncytotoxic at all doses tested. In contrast, the N-hydroxy derivatives of each aromatic amide were highly cytotoxic, as were the ester compounds. For each active derivative, the slope of the survival curve for XP2BE was 2-2.k times steeper than that of the normally repairing strain.
J Natl Cancer Inst 1975 Jun
PMID:Cytotoxicity of carcinogenic aromatic amides in normal and xeroderma pigmentosum fibroblasts with different DNA repair capabilities. 113 46

The reactions to monochromatic radiation of the skin of ten patients with xeroderma pigmentosum were investigated, and eight were abnormal. The abnormalities consisted of papular and vesicular reactions and delay in the development of the minimal erythema dose reaction with wavelengths principally in the 290-320 nm range. Three patients were too young for full action spectra to be obtained but of those patients in whom all wavelengths were tested only one showed a reaction to radiation above 320 nm and this was at 340 nm only. In only one patient was the minimal erythema dose at 300 nm at 24 h lower than normal. In six patients the repair synthesis of deoxyribonucleic acid after ultraviolet radiation was estimated. Reduced levels were seen in five but repair was normal in one patient. The patient with normal repair also had normal reactions to monochromatic radiation. The abnormal reaction of the skin to artificial radiation and the abnormal deoxyribonucleic acid repair synthesis may enable the diagnosis of xeroderma pigmentosum to be made at a very early age. In one of the patients the diagnosis was made at the age of 6 months in a child with photosensitivity but with no other clinical signs of the disease. It is suggested that, by making the diagnosis as early as possible and by protecting the skin from natural sunlight, cutaneous malignancies may be prevented.
 ...
PMID:The erythemal action spectrum and deoxyribonucleic acid repair synthesis in xeroderma pigmentosum. 115 44

The activation of the mycotoxins aflatoxin B1, G1, B2, G2, aflatoxicol and sterigmatocystin by 9S fraction, microsomal preparation (105,000 times g) and supernatant (105,000 times g) of livers of several species was examined. DNA repair synthesis, chromosome aberrations and clone forming capacity were used as endpoints. Cultured fibroblasts of normal persons and DNA repair deficient Xeroderma pigmentosum patients were employed as test subjects. The activation mixtures significantly increase the chromosome breaking function, lethality and DNA damaging effect (measured as DNA repair synthesis) of aflatoxin B1, G1, aflatoxicol ans sterigmatocystin. The DNA repair-deficient XP cells respond to the activated mycotoxins with a low level of unscheduled 3HTdR incorporation as compared to that of control cells, but show a highly elevated sensitivity to the chromosome-damaging and lethal effect of aflatoxin B1 and sterigmatocystin.
Int J Cancer 1975 Aug 15
PMID:The response of Xeroderma pigmentosum cells and controls to the activated mycotoxins, aflatoxins and sterigmatocystin. 117 27

Microcell-mediated chromosome transfer (MMCT) is a powerful genetic technique that permits the transfer of a single chromosome from one mammalian cell to another. The utility of MMCT for gene mapping strategies is critically dependent on the careful characterization of the chromosomes being transferred. We have recently reported the identification of a single rearranged human chromosome, designated Tneo, which corrects the UV sensitivity and excision repair defect of cells of xeroderma pigmentosum genetic complementation group D (XP-D) in culture (Flejter WL et al., Proc Natl Acad Sci USA 89:261-265, 1992). Additionally, those studies demonstrated a role for the excision repair cross-complementing 2 (ERCC2) gene in the observed phenotypic correction. We now report the results of detailed conventional and molecular cytogenetic characterization of the complementing Tneo chromosome. This analysis revealed a complex rearrangement involving material from human chromosomes 16, 17, and 19. Characterization of deletions of Tneo which retained or lost XP-D complementing ability mapped the gene responsible for phenotypic correction to a small region of the terminal q-arm of this chromosome. This region includes the previously described human DNA repair gene cluster located in the region 19q13.2-q13.3, a result consistent with the notion that the in vitro correction of XP-D cells by the Tneo chromosome is rendered by the ERCC2 locus. The data illustrate the potential value of detailed cytogenetic characterization of a human chromosome present in a somatic cell hybrid, even when that material involves complex rearrangements.
Genes Chromosomes Cancer 1992 Nov
PMID:Characterization of a complex chromosomal rearrangement maps the locus for in vitro complementation of xeroderma pigmentosum group D to human chromosome band 19q13. 128 22

Constitutional loss or inactivation of one copy of a tumor-suppressor gene, as exemplified by hereditary retinoblastoma, increases the propensity for malignancies by reducing the number of events necessary for the complete loss of the negative regulatory function. We developed a selectable mutation assay employing a human lymphoblastoid cell line (LCL) derived from a heterozygous carrier of 2,8-dihydroxyadenine urolithiasis, adenine phosphoribosyltransferase (APRT) deficiency, for dissecting the second step in loss-of-function mutations and for determining the potential of physical and chemical agents for producing such mutations. The mode of mutational events arising in the wild-type allele of the functionally heterozygous APRT gene resembled that reported for tumor-suppressor genes in malignancies in that mitotic non-disjunctions or recombinations as well as deletions prevailed. Ultraviolet light (UV) was much less efficient in inducing these types of mutations than ionizing radiation. A group of autosomal recessive cancer-prone diseases, including xeroderma pigmentosum (XP), has been characterized as being more susceptible to genomic insults, owing to some defects in DNA processing, such as replication, repair, or recombination. This increased genomic instability may accelerate the gain-of-function mutation at a proto-oncogene and/or the loss-of-function mutation at a tumor-suppressor gene. XP complementation group A (XP-A) LCLs were extremely sensitive to UV-mutagenesis at the hypoxanthine phosphoribosyltransferase (HPRT) locus even at equicytotoxic doses. Some unique mechanism may operate in UV-mutagenesis in XP-A. We have succeeded for the first time in rendering XP-A cells tumorigenic in athymic mice by applying multiple exposures to UV and subsequent treatment with TPA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Molecular bases for hereditary cancer-prone diseases. 129 55

In Japan, more than 400 patients with xeroderma pigmentosum (XP) have been registered. The major groups are XP-A and variant, while clinically mild types of XP with intermediate levels of unscheduled DNA synthesis (UDS) have recently been increasing. The classical type of XP-A and some of the XP-D patients exhibit neurologic abnormalities. XP individuals display a marked increase in the frequency of skin malignancy. Development of skin malignancies appears to be related to the level of DNA repair capacity; the lower the capacity, the earlier and more frequently the skin tumors develop. Furthermore, the incidence of internal malignancy in XP patients is at least ten times higher than that for the Japanese general population over the age of 40 years. Cultured fibroblasts from XP patients exhibit higher sensitivity not only to UVC but also to UVB. The cellular sensitivity to UVB may correlate to photosensitivity in vivo from a study on a group E patient who showed age-related changes in photosensitivity and cellular sensitivity to UVB. We have also reviewed current status of molecular genetics in XP.
 ...
PMID:Xeroderma pigmentosum: recent clinical and photobiological aspects. 129 56

In the course of a chromosome fragility investigation on the cancer prone hereditary disorder xeroderma pigmentosum, a low proportion of cells with a 47,XY,+21 karyotype was found in lymphocyte cultures of a patient not showing any Down syndrome symptom. The presence of trisomy 21 mosaicism was demonstrated also in peripheral blood of the healthy father and confirmed by "chromosome painting" that allowed a rapid detection of chromosomes 21 on metaphase cells and interphase nuclei. The trisomic cell line was not detected in fibroblast cultures. The analysis of chromosome 21 heteromorphism indicated that in both subjects the mosaic could result from either a diploid or an aneuploid zygote. Since in the trisomic cell line of the father and the son the extra chromosome 21 seems to be the same, a predisposition toward mitotic errors (non-disjunction or anaphase lagging) may be postulated, leading to the recurrent gain or loss of a specific chromosome 21. In order to test the hypothesis of an abnormal mitotic behaviour of the chromosome 21, we investigated the centromere separation index and the DNA restriction pattern in Southern blots probed with satellite DNA sequences specific for chromosome 21 centromere. Both the approaches did not reveal any peculiar feature that may account for the genetically determined proneness to mitotic error observed in the family.
 ...
PMID:Trisomy 21 mosaicism in two subjects from two generations. 129 25


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