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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms of UV-induced ageing and carcinogenesis of the skin have been elucidated in animals and humans, and both UVB and UVA radiation have been shown to have deleterious effects on the skin. Thus the use of solaria which deliver mostly UVA radiation is not safe. There is also an increased risk of ageing when using therapeutic UV sources. UV radiation is beneficial in many cases of skin disorders such as psoriasis, atopic eczema, acne and pruritus. Nevertheless by careful patient selection and follow-up the risks of UV can be minimised when treating patients with artificial UV radiation. During recent years there has been intensive research into the development of agents which prevent harmful effects of radiation. The retinoids are particularly interesting as they enhance skin repair after UV damage, have an anticarcinogenic effect and are effective for treating precancerous lesions such as solar keratosis and as adjuvant therapy for skin cancers. Topical retinoids are already used for the treatment of actinic skin damage, and systemic retinoids are also used in certain groups of patients who have an increased risk of contracting skin cancers such as xeroderma pigmentosum.
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PMID:Ultraviolet radiation in skin ageing and carcinogenesis: the role of retinoids for treatment and prevention. 175 19

We showed previously that the persistence of chromatid breaks and gaps after G2 phase irradiation with X-rays or near-UV visible light characterizes skin fibroblasts from individuals with cancer-prone genetic diseases. This abnormal response appears to result from deficient DNA repair during G2 and to be associated with cancer proneness. We have, therefore, compared the responses of cells from two genetic disorders, Cockayne syndrome (CS) and xeroderma pigmentosum complementation group C(XP-C), both of which exhibit cellular hypersensitivity to sunlight, but only one of which, XP, manifests a high rate of sunlight-induced cancer. CS cells, in contrast to XP cells, showed a normal G2 response to irradiation with either X-rays or near-UV visible light. However, CS cells showed a deficiency in repair of DNA damage inflicted by light during S and G1 phases of the cell cycle. The present results support the concept that deficient DNA repair during G2 phase plays a role in carcinogenesis. This deficient repair in the presence of DNA damage and continuous cell cycling from activation of proto-oncogenes or loss of suppressor genes may be necessary and sufficient for cancer development.
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PMID:Radiation-induced chromatid aberrations in Cockayne syndrome and xeroderma pigmentosum group C fibroblasts in relation to cancer predisposition. 175 75

The chemical integrity and proper functioning of DNA is threatened by numerous chemical and physical agents that cause a wide spectrum of DNA lesions. When unrepaired, DNA injury interferes with vital, cellular functions such as DNA replication and transcription and give rise to mutations leading to genetic defects, carcinogenesis and cell death. The contribution of DNA repair systems in preventing cancer is apparent from the high rate of tumorigenesis found in many repair syndromes. A classical example is the excision repair disorder xeroderma pigmentosum (XP) in which patients exhibit hypersensitivity to sun (UV) light and predisposition to skin cancer. Genetic analysis of cultured cells from XP patients has revealed the presence of at least 7 complementation groups, all showing a deficiency in the excision of UV-induced lesions in the DNA. To identify the genes and characterize the genetic defects in these complementation groups, cloning of human DNA repair genes has been attempted by a number of investigators. Recently, the first human DNA repair genes have been cloned including at least two genes involved in XP. Comparison of the coding sequences of these genes with sequences of cloned (repair) genes of lower organisms (e.g. E. coli and yeast) provides information on their function. This leads to understanding of the relationship between molecular defect at the level of the gene and the gene product and the clinical manifestation of the disease in different XP patients and complementation groups.
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PMID:The genetic basis of xeroderma pigmentosum. 180 20

It has long been recognized that exposure to specific chemical and physical agents can result in the appearance of tumours in both man and animals. There is substantial evidence that DNA is the ultimate cellular target of carcinogens and that DNA repair is an important cellular defence against the effects of carcinogen exposure. Some insight into the molecular processes involved in cellular responses to carcinogens is provided by the occurrence of rare human disorders that display complex abnormalities in processing DNA damage or maintaining genomic integrity. These disorders include xeroderma pigmentosum, Cockayne syndrome, ataxia telangiectasia, dysplastic nevus syndrome and Bloom syndrome. Such disorders have provided clues to some of the basic mechanisms involved in carcinogenesis.
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PMID:Carcinogenesis: molecular defences against carcinogens. 186 47

The time course of DNA repair, using (3H)thymidine uptake as parameter, was measured during 8 h after a single exposure to 2, 8, and 16 UV-C J/m2 in lymphocytes of 8 cancer patients, 1 xeroderma pigmentosum patient and 10 controls. All patients had reduced repair, and all controls normal repair, as calculated 2 h after a single exposure. Six patients reached normal levels with a delay of 2-6 h, whereas 2 patients and the xeroderma pigmentosum patient did not. Although the kinetic curves in controls and patients had a similar form, those for 8 and 16 J/m2 in patients were shifted so that they corresponded to that of 2 J/m2 in controls. Additionally the ability to repair repeated damage (cells irradiated twice or three times at 2-hour intervals with doses of 2 or 8 J/m2) was investigated in 6 patients and in 7 controls. The incorporation values showed significant differences between patients and controls at each dose and time point. Cancer patients tend to repair repeated damage less efficiently than controls. Using these parameters subtle differences between the repair ability of individuals might be identified. Because of the known connection between reduced DNA repair and carcinogenesis, this might help to distinguish cancer-prone individuals.
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PMID:Differences in the kinetics of DNA repair in cancer patients and healthy controls. 189 Nov 74

A variety of clinical, topographical, histological, epidemiological and geographical arguments attribute to the effects of solar radiation and to ultraviolet rays (UV) in particular, a decisive role in the processes of cutaneous carcinogenesis. This carcinogenicity is part of a series of chronic changes affecting the integument which constitute heliodermatitis or photosenescence. The effects of UV are cumulative. DNA is the main target of UV rays. Man possesses several DNA repair systems. The hereditary malfunction of part of these systems result in xeroderma pigmentosum, which constitutes a pathological model of photocarcinogenesis. Intrinsic skin ageing (non-photodependent) appears to promote this process of photocarcinogenicity by several mechanisms: summation of DNA changes, progressive deterioration of repair systems, dermal-epidermal atrophy, melanocytic changes, immuno-surveillance deficit.
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PMID:[Cutaneous senescence and carcinogenesis]. 189 73

Xeroderma pigmentosum is a rare inherited dermatosis that provides insight into the basic mechanism of carcinogenesis. It is a model disorder linking defective DNA repair with clinical abnormalities and neoplasia. UV light-induced damage to the skin begins early and results in multiple benign and malignant skin tumors, especially in sun-exposed areas of the head and neck. Oral cancers, primarily squamous cell carcinomas of the anterior third of the tongue, occur with greatly increased frequency. A patient with multiple facial neoplasia and oral manifestations of xeroderma pigmentosum is presented. The role of the dentist in surveillance of oral and perioral structures is emphasized. The dentist is advised against the use of UV light-curing units in these patients because UV-induced epithelial damage may cause dysplasia when DNA repair mechanisms are dysfunctional.
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PMID:Xeroderma pigmentosum: review and report of a case. 201 52

DNA repair in mammals consists of a large family of genes that encode a variety of mutually interacting gene products. These gene products coordinately locate and prepare damaged sites in chromatin for eventual excision and replacement and interact with transcriptionally active and replicating regions. Subsets of repair genes are represented by the complementation groups of xeroderma pigmentosum (XP), Cockayne syndrome, trichothiodystrophy and the ERCC series, which overlap one another to varying degrees. Cloned DNA sequences or whole chromosomes correct the UV-sensitive phenotype of XP by only 6-50%, which may be informative for the precise mechanisms of complementation and repair and for the relative importance of various UV photoproducts. Repair deficiencies in vivo are associated with increases in the toxic effects of UV damage and chronic expression of damage-inducible genes, with consequent implications for viability, development, neurological and immunological function, and carcinogenesis.
Carcinogenesis 1990 Jun
PMID:Do we know the cause of xeroderma pigmentosum? 218 96

The genetic factors involved in the multistep process of carcinogenesis can be divided at least into two major categories: 1. Mutated or lost genes, which may directly represent one step in the sequential process (tumour suppressor genes); inheritance of one tumour suppressor gene causes dominant expression of the carcinogenic phenotype (the dominant inheritance is described in the accompanying paper); 2. Other genes, which lead to conditions that favour the development of cancer and generally are inherited in a recessive fashion; they are the subject of this paper. Autosomal recessively inherited diseases, such as xeroderma pigmentosum, ataxia-telangiectasia, Bloom's syndrome and Fanconi's anaemia display increased genome instability (chromosomal fragility and/or DNA-repair deficiencies) and are associated in the homozygote and probably also in the heterozygote state with defined malignancies. Neoplasms particularly of the lymphoreticular system frequently occur in patients with genetically determined immunodeficiencies (e.g. severe combined immune deficiency or Wiskott-Aldrich syndrome). People differ due to their individual genetic constitution in their responses to various classes of carcinogens such as physical and chemical agents, to dietary habits, as well as to viruses. Furthermore, tumours are often found in patients displaying premature aging (e.g. Werner's syndrome). In addition, several metabolic abnormalities such as genetic syndromes featuring chronic liver disease, but also many other inherited metabolic conditions have cancer as a regular or frequent complication.
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PMID:Recessively inherited deficiencies predisposing to cancer. 219 May 29

Cells from patients with the cancer-prone inherited disease, xeroderma pigmentosum (XP) are known to be defective in the endonuclease-mediated incision step in excision repair of a number of different types of DNA adducts, but the molecular events responsible have not been delineated. We have previously reported isolation of two DNA endonucleases, pI 4.6 and 7.6, from normal human chromatin which recognize adducts produced by psoralen plus long wavelength ultraviolet radiation (UVA). These endonucleases are both present in XP complementation group A (XPA) cells even though these cells are hypersensitive to this type of damage. We now report that introduction by electroporation of either normal endonuclease into XPA cells restored their markedly deficient DNA repair-related unscheduled DNA synthesis (UDS) to higher than normal levels following exposure to psoralen plus UVA. Introduction of XPA endonucleases into similarly treated XPA cells had little or no restorative effect on UDS. However, both normal and XPA endonucleases increased UDS in normal cells to higher than normal levels. These results indicate that XPA cells have endonucleases which can repair these adducts but which cannot function in intact cells unless a factor(s), which they lack is provided by normal cells.
Carcinogenesis 1990 Mar
PMID:Electroporation of normal human DNA endonucleases into xeroderma pigmentosum cells corrects their DNA repair defect. 231 Nov 96


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