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)

DNA single-strand breakage by bleomycin treatment of cultured mammalian cells was demonstrated by the method of alkaline elution. Elution patterns from treated L1210 cells indicated that part of the DNA was extensively broken while the remainder was affected to a lesser degree. This biphasic effect, which was less prominent in human fibroblasts, may reflect a selective sensitivity either of part of the cell population or of part of the DNA within individual cells. In both cell types, the DNA damage was at least partially repaired upon incubation of the cells after removal of drug. Bleomycin did not inhibit the rejoining of X-ray-induced single-strand breaks. The production and repair of DNA single-strand breaks after bleomycin treatment were the same in normal human and xeroderma pigmentosum fibroblasts, indicating that these events do not require the excision endonuclease that appears to be defective in these ultraviolet light-sensitive xeroderma cells.
Cancer Res 1976 Oct
PMID:Single-strand scission and repair of DNA in mammalian cells by bleomycin. 6 Jan 74

Peripheral blood lymphocytes from four patients with ataxia telangiectasia (AT), an inherited disorder showing, among other features, radiosensitivity and a high frequency of cancers, were shown to be cytogenetically more sensitive to bleomycin than were lymphocytes from both normal individuals and a single patient with xeroderma pigmentosum. With cell survival techniques, a biphasic dose-response curve was seen for both normal and AT fibroblasts, although the AT cells showed a much lower survival. The increased sensitivity to bleomycin in AT cells might be expected since it is a radiomimetic drug, but more importantly the known action of bleomycin in producing DNA strand scission suggests that AT cells might be defective in rejoining a proportion of DNA strand breaks.
Cancer Res 1979 Mar
PMID:Unusual sensitivity of ataxia telangiectasia cells to bleomycin. 8 79

DNA excision repair was measured in cultured human fibroblasts after single or dual treatments with ultraviolet radiation, 4-nitroquinoline 1-oxide, or N-acetoxy-2-acetylaminofluorene. Three approaches were used to monitor repair: unscheduled DNA synthesis, measured by autoradiography; repair replication, measured by the incorporation of a density-labeled DNA precursor into repaired regions; and excision of ultraviolet endonuclease-sensitive sites. When a single repair- saturating dose of one of the three carcinogens was administered, little stimulation of unscheduled DNA synthesis or repair replication could be observed by additional treatment with one of the other carcinogens. In no instance was total additivity of repair observed. These observations were confirmed by showing that the excision of endonuclease-sensitive sites produced by ultraviolet damage (i.e., pyrimidine dimers) was inhibited by exposure to 4-nitroquinoline 1-oxide and N-acetoxy-2-acetylaminofluorene. The data indicate that the repair of lesions induced by these substances may have common rate-limiting steps, a conclusion previously indicated by the repair deficiency in xeroderma pigmentosum cells in which a single mutation eliminates the repair of damage caused by each of these agents.
Cancer Res 1979 Jul
PMID:Overlapping pathways for repair of damage from ultraviolet light and chemical carcinogens in human fibroblasts. 10 94

Among various strains of skin fibroblasts tested, two strains derived from xeroderma pigmentosum (XP) patients (ages 19 and 25) with neurological complications and two strains obtained from heterozygotes (ages 54 and 18) showed relatively higher susceptibility than normal age-matched controls to transformation by feline sarcoma virus (FSV). Only one strain from a normal individual also showed a high susceptibility. Generally, there was a parallelism in susceptibilities to FSV and Kirsten murine sarcoma virus (KiMsv). However, cells from normal individuals of 46 years or older exhibited high ratios of FSV:KiMSV titers which were due to their lower susceptibility to KiMSV. Cells from two XP patients (ages 25 and 22) and a heterozygote (age 18), who were in a younger age group, manifested such a differential susceptibility to FSV and KiMSV. There was a correlation between the relative sensitivity of XP cells to the cytotoxic effect of 4-nitroquinoline 1-oxide and killing effect of UV light. Pretreatment of fibroblasts from three XP patients by a subtoxic dose of 4-nitroquinoline 1-oxide 24 hr before viral infection facilitated transformation by KiMSV and FSV, whereas no such effect was observed with three normal cells strains similarly treated.
Cancer Res 1976 Sep
PMID:Susceptibility of xeroderma pigmentosum cells to transformation by murine and feline sarcoma viruses. 18 47

Repair replication was examined in cultured human cells exposed to the hepatocarcinogen aflatoxin B1 using the combined bromodeoxyuridine density label and radioisotopic label method. Semiconservative DNA synthesis was strongly inhibited, and the repair replication mode was stimulated in diploid fibroblasts (W138) and in their SV40 transformants (VA13) only when exposure to aflatoxin B1 was in the presence of an activating system containing rat liver microsomal enzymes. The maximum amount of repair synthesis was about 20% of that obtained after saturating doses of ultraviolet light (UV). The time course of repair synthesis was similar to that seen after UV, and most of the synthesis was in 30- to 50-nucleotide "short patches." A line of SV40-transformed xeroderma pigmentosum cells (Group A) deficient in repair after exposure to UV was similarly deficient in repair replication after aflatoxin treatment. Treatment with aflatoxin resulted in a 25 to 45% inhibition of UV-induced repair replication, suggesting that in addition to producing lesions in DNA, which are substrates for the excision repair system, the toxin also inhibits excision repair. CsC1 gradients of DNA treated in vitro with activated aflatoxin demonstrated binding of the drug to DNA. Alkaline sucrose gradient sedimentation gave no indication that single-strand breaks or alkali labile bonds were introduced into DNA by treatment of cells with activated aflatoxin.
Cancer Res 1977 Jun
PMID:Repair of DNA in human cells after treatment with activated aflatoxin B1. 19 62

Nine lymphoblastoid cell lines were established after transformation by Epstein-Barr virus of peripheral lymphocytes from four xeroderma pigmentosum (XP) patients, the parents of one XP patient, and three normal donors. All these cell lines proliferate as suspension in Roswell Park Memorial Institute Medium 1640 supplemented with 20% fetal bovine serum, without detectable release of infectious Epstein-Barr virus. Some characteristics of these cell lines, such as growth rates, chromosome numbers, UV sensitivities, and activities of unscheduled DNA syntheses induced by UV, 4-nitroquinoline 1-oxide, and N-methyl-N'-nitro-N-nitrosoguanidine, were determined. Results confirm that the properties related to XP are not altered by transformation with Epstein-Barr virus and are the same in degrees of defect as are those of dermal fibroblasts from the respective individuals. These XP and normal lymphoblastoid cell lines should be especially useful for biochemical studies on the mechanism of DNA repair, because they are easy to grow in mass culture.
Cancer Res 1978 Feb
PMID:A convenient method of establishing permanent lines of xeroderma pigmentosum cells. 20 81

Ten lymphoblastoid cell lines were established by Epstein-Barr virus-induced transformation directly from 0.04 to 0.15 ml of peripheral whole blood of one patient with xeroderma pigmentosum and four normal healthy adults. All these lines expressed B-lymphocyte characteristics. The advantages of this method are: (a) only a few drops of blood are required for establishing a permanent line; (b) damage and loss of cells in separation procedures are minimal; and (c) the method is simple, reliable, and applicable, if desired, to any patient, even babies.
Cancer Res 1978 Oct
PMID:A greatly simplified method of establishing B-lymphoblastoid cell lines. 21 Sep 42

When confluent human skin cultures are ultraviolet (UV)-irradiated before infection with Herpes Simplex type 1 virus (HSV), their capacity to support virus growth is impaired. When the time interval between UV-exposure and infection is increased up to 36 hours, different recoveries of HSV production capacity are observed according to the origin of the host cells. 1) Two normal donors: the cells present a dose dependent recovery which is maximal for a dose ( : formula: (see text) at which a plateau level of unscheduled DNA synthesis (UDS) is reached. 2) A mother of two Xeroderma Pigmentosum (XP) children: in this line which exhibits a normal level of UDS, the extent of recovery is significantly decreased after exposures : formula: (see text) 3) An XP child: these cells have a normal level of UDS (XP variant) whereas they present a low extent of recovery as compared with that of the normal subjects. 4) Five XP children: in these excision deficient lines (UDS less than 15%), HSV production capacity decreases with increasing time intervals after UV exposure for doses greater than or equal to 3 : formula: (see text). For doses less than 3 : formula: (see text), a small recovery with an overshoot of viral production is observed 24 h after UV exposure in the lines (three) which present the highest UDS (10--15%) and not in the two lines which present a very low UDS (1--2%).
Bull Cancer 1978
PMID:Herpes virus production as a marker of repair in ultraviolet irradiated human skin cells of different origin. 21 90

The role of DNA repair in transformation was investigated by infecting repair-deficient xeroderma pigmentosum (XP) variant cells, XP variant heterozygous cells, and normal human fibroblasts with simian virus 40 which had been irradiated by ultraviolet light. The transformation frequencies obtained were compared to those observed for unirradiated virus. While normal and heterozygous cells showed no differences between transformation frequencies using either irradiated or untreated virus, two XP variant cell lines were transformed 2- to 7-fold more readily with irradiated virus than with unirradiated virus. XP variant cells were also found to produce lower than normal quantities of virus following infection with either damages or undamaged virus, suggesting that increased viral production was not contributing to the increased transformation seen for these cells. Finally, the proportion of cells which repair ultraviolet light-irradiated simian virus 40 was found to be similar for wild-type and XP variant cells, suggesting that enhanced transformation in the mutant cells was not associated with a reduction in the numbers of cells which repair damaged virus. Several possible mechanisms to account for the increased transformation of XP variant cells by ultraviolet light-irradiated simian virus 40 are proposed.
Cancer Res 1979 Oct
PMID:Enhanced transformation of xeroderma pigmentosum variant cells by ultraviolet light-irradiated simian virus 40. 22 15

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


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