Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xeroderma pigmentosum (XP), Fanconi anaemia (FA), ataxia telangiectasia (AT) and Bloom disease (BS) are four rare autosomal recessive disorders in which there is defective DNA repair and/or chromosome instability and proneness to malignancy. Between 80 and 90% of patients with XP have a defect, demonstrable at cell level, of excision of DNA lesions induced by ultraviolet rays, while the remainder have a cellular error of post-replication repair. XP cells are also deficient in repairing DNA damage caused by a variety of chemical mutagens. There are at least five different complementation groups of the first, or classical, type of XP (A to D, etc.) Apparently group C patients, as well as those with defective post-replication repair, do not show the progressive neurological illness found in a proportion of the other patients. AT is heterogeneous clinically and genetically. Clinically it presents with a progressive neurological illness, progressive telangiectases and a developmental disorder of the thymus. AT is characterized by sensitivity to X-rays and AT cells are unable to repair gamma-ray-induced damage to bases in the DNA. It appears that in many cases of the disorder a chromosomally marked cellular clone is found. In BS the main defect, which results in growth retardation, sun-induced lesions of the face and susceptibility to infection, appears to be a slow DNA chain maturation during DNA synthesis. An increase of sister chromatid exchanges is characteristically seen in the chromosomes of cultured BS cells. In FA, in which there is progressive pancytopenia with eventual bone marrow exhaustion and a tendency to haemorrhage and infection, the cellular defect seems to consist of faulty removal of repair of cross-links in the DNA. In this condition, as in BS and AT, various structural chromosome changes are detected in cultured cells. Patients with XP develop skin cancers in early life and often maligant melanomas. In the other three disorders, in which an immune deficiency is often present, leukaemia and related proliferative disorders are a frequent cause of death while other malignancies also occur. There is some evidence that points to an increased risk of malignancy in heterozygotes who carry the FA and AT genes.
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PMID:DNA repair defects and chromosome instability disorders. 25 77

Several autosomal recessive diseases are associated with apparent DNA repair defects in cell culture. It seemed likely that a defect in excision repair reported for ataxia telangiectasia cells might reflect a lack of apurinic endonuclease activity. We report here normal levels of apurinic endonuclease activity in extracts of cell lines derived from patients with ataxia telangiectasia, xeroderma pigmentosum (complementation group D), Cockayne dwarfism, Fanconi anemia and Bloom syndrome.
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PMID:Apurinic DNA endonuclease activities in repair-deficient human cell lines. 63 94

Several observations reported in the literature suggest that singlet oxygen (1O2) might play a role in the clastogenic process in Fanconi anemia (FA) cells, and that the antioxidant status of xeroderma pigmentosum (XP) may also be altered. In order to test the ability of FA and XP cells, relative to normal cells, to cope with 1O2 damage, the effects of photosensitization by hematoporphyrin (HP) have been determined (i) on host cell reactivation (HCR) of damaged infecting herpes simplex virus (HSV) or transfecting SV40 DNA, and (ii) on DNA template capability and clonogenicity of treated cells. Results showed no significant difference among the three types of cells, either for the survival of HP-photosensitized HSV, or for the yields of SV40 virus following transfection of cultures with damaged viral DNA. The treatment of cells with HP plus 365-nm light leads to a dose-dependent, homothetic reduction of 18S and 28S ribosomal RNA (rRNA) synthesis, presumably through a mechanism other than the formation of transcription termination sites. After a 24-h post-exposure incubation, the rate of rRNA synthesis was restored to higher than normal levels in all cell lines. Finally, two FA cell lines showed a higher survival to HP photosensitization than two normal cell lines. Another FA cell line and XP-A and XP-C cells were in the range of sensitivity of the two normal strains for this treatment. These results indicate that FA cells possess an antioxidant defense system at least as efficient as that of normal cells for processing 1O2-induced damage.
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PMID:Cellular responses to hematoporphyrin-induced photooxidative damage in Fanconi anemia, xeroderma pigmentosum and normal human fibroblasts. 128 Dec 79

We have used a host cell reactivation system to study the effect of 8-methoxypsoralen (8-MOP) reaction on CAT (chloramphenicol acetyltransferase) and NEO (aminoglycoside phosphotransferase) expression in normal human cells, as well as two cell lines with possible DNA repair-processing defects. Plasmid DNA was treated with psoralen plus near-ultraviolet (NUV) irradiation. The reacted plasmids, pSV2cat and pSV2neo, were transfected into Fanconi anemia (FA), xeroderma pigmentosum (XP), and normal human fibroblast cells for transient or stable assay. The cells were assayed for CAT activity at various times after transfection or selected for G418 resistance. The extent of adduct formation required to inhibit expression was much less (difference of D37 greater than 2.5) in FA or XP cells compared to normal. We conclude that in FA and XP cells, the reactivation of CAT was much less than in normal cells. The possibility of differential DNA uptake and/or degradation in transient assay was ruled out by analysis of plasmid DNA recovered from transfected cells. The data of the two independent assays indicate that FA and XP cells are deficient in cross-linked DNA repair.
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PMID:Reactivation of psoralen-reacted plasmid DNA in Fanconi anemia, xeroderma pigmentosum, and normal human fibroblast cells. 204 39

The present studies confirm that diesel exhaust emissions are mutagenic in bacterial and mammalian mutation assays. Our results further indicate that mutagenic potential of the diesel tar samples can be reduced by exogenous metabolic activation with S15, and that Epstein-Barr-virus transformed lymphoblastoid cell lines from Bloom syndrome, and Xeroderma Pigmentosum patients with a high incidence of malignant tumors showed an larger production of SCEs while those from Fanconi anemia patients had an lower frequency of SCEs when exposed to the diesel emission condensate, compared to those from normal healthy persons. On the contrary to the results of in-vitro studies, the in-vivo SCE and micronucleus assays using mouse and rat bone marrow cells gave negative responses.
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PMID:Genotoxicity of diesel exhaust emissions in a battery of in-vitro short-term and in-vivo bioassays. 243 8

We have evaluated the ability of immortalized human fibroblasts to recombine transfected plasmid DNA. A number of cell lines from normal individuals and from patients with DNA damage-processing defects were examined. Two plasmid recombination substrates were derived from pSV2neo and contained nonoverlapping deletions in the aminoglycoside phosphotransferase II gene. Intermolecular recombination was assessed by two methods after cotransfection. In a short-term, extrachromosomal recombination assay, low molecular weight DNA was extracted from the human cells 48 h after transfection, and recombinant plasmids were detected by transformation into appropriate indicator bacteria. In a long-term stable recombination assay the fibroblasts were cotransfected and G418-resistant colonies allowed to form. By the former assay all but two cultures were recombination-proficient, whereas all were recombination-proficient by the latter assay. The efficiency of transfection of human cells with plasmids appears to be a major variable affecting recombination. Recombination can be stimulated by uv irradiation of plasmid DNA prior to transfection. Cells from patients with Fanconi anemia, ataxia telangiectasia, and xeroderma pigmentosum complementation groups A, C, D, E, and G are not defective at intermolecular plasmid recombination.
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PMID:Intermolecular plasmid recombination in fibroblasts from humans with DNA damage-processing defects. 255 Sep 80

We report two first cousins with xeroderma pigmentosum who developed a refractory anaemia with excess of blasts which resulted in their deaths.
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PMID:Xeroderma pigmentosum and refractory anaemia in two first cousins. 261 Nov 27

DNA repair in man can be described in general terms, but details are still obscure. Excision repair of base damage has a general similarity to the mechanism of the bacterial uvr ABC exonuclease, but the individual roles of at least 15 genes that regulate mammalian excision repair are as yet unknown. The differential repair of specific regions of DNA and of specific genes is highlighted by the clustered mode of repair characteristic of xeroderma pigmentosum group C and by the rapid repair of the dihydrofolate reductase gene. Cloning of genes that specify repair in man is proceeding slowly, in part, because of confusion by genes that produce only partial correction or nonspecific changes in sensitivity and by phenotypic reversion. In human cells, DNA damage-inducible genes are recognized that may overlap the spectra of other stress-induced proteins, but the relationship of these to any error-prone or recA-like system is unknown and unlikely. Four diseases, xeroderma pigmentosum, ataxia telangiectasia, Cockayne syndrome, and Fanconi anemia, have well-documented and significantly increased sensitivities to DNA-damaging agents, and each has recognizable though complex abnormalities in processing DNA damage. In addition, a wide variety of diseases and cellular processes have been ascribed to an association with DNA damage and repair, but the accuracy and significance of these associations are hard to identify.
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PMID:DNA repair in man. 265 41

Chromosome alterations, which are directly visible changes in the DNA, have close associations to cancer development, non-specific ageing, and heritable genetic status. Human lymphocyte cultures can be used for cytogenetic monitoring of genetic health because many cancers and genetic effects are caused by long-term unhealthy life-styles. We have investigated the sensitivities of lymphocytes from inherited-cancer-prone diseases to the induction of the chromosome alterations by mutagens and carcinogens, and the correlations between the frequency of sister chromatid exchanges (SCEs) in peripheral lymphocytes and life-styles or daily ways of living. Lymphocytes from patients with Down syndrome, Fanconi anemia, xeroderma pigmentosum, ataxia telangiectasia, and Bloom syndromes showed altered (usually enhanced) susceptibilities to the induction of chromosome aberrations and SCEs by mutagens and carcinogens in our environments. Mean frequencies of baseline SCEs in lymphocytes from normal men with poor life-styles have also been shown to be significantly higher than those in cells from men having good life-styles. The former cells have further been shown to have hyper sensitivities to the induction of SCEs by mitomycin-C' treatment compared to latter cells. Unhealthy life-styles also make the lymphocytes to be more sensitive to ara-C's enhancement of radiation-induced chromosome aberrations.
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PMID:[Sister chromatid exchanges and chromosome aberrations as parameters for human risk of cancer development]. 295 45

Fibroblasts from patients with xeroderma pigmentosum (XP) complementation groups A, C, D, E, and G, as well as Bloom syndrome (BS) and Fanconi anemia (FA) have been transfected with a plasmid, pSV7, containing the early region of Simian virus 40 (SV40). All of the cultures exhibited cytologic changes characteristic of transformed cells and expressed T-antigen. They also contained integrated copies of DNA derived from the vector, and in several cases, extrachromosomally replicated DNA. Not all of the transfected cultures became immortalized. The transformed xeroderma pigmentosum (XP) cultures retained their UV-sensitive phenotype in all but one case. The BS and FA cell lines retained their characteristic phenotype. All of the cultures, except the BS cells, can be readily transfected with the plasmids, pSV2neo and pSV2gpt.
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PMID:Transformation of DNA repair-deficient human diploid fibroblasts with a simian virus 40 plasmid. 303 Jul 88


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