{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T04:18:00Z","timestamp":1767500280317,"version":"3.48.0"},"reference-count":57,"publisher":"The Royal Society","issue":"1188","license":[{"start":{"date-parts":[[1981,7,14]],"date-time":"1981-07-14T00:00:00Z","timestamp":363916800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1981,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Several human syndromes are described with which have been associated a deficiency in the ability to repair damage to cellular DNA. This deficiency is generally manifested as a sensitivity to DNA-damaging agents such as u. v. light, ionizing radiation, or psoralen photosensiti\u00adzation (PUVA). In xeroderma pigmentosum (XP) a high frequency of light-induced skin cancers is correlated with hypermutability of fibro\u00adblasts following u. v. irradiation in vitro, providing telling support for the somatic mutation theory of cancer. Closer inspection, however, reveals that a pseudopromoting action of light or PUVA may be equally import\u00adant in skin carcinogenesis in both XP and normal individuals. It is suggested that impairment of cell-mediated immune response in the skin (possibly by DNA damage) may be responsible for this pseudopromoting action. That more than an enhanced frequency of somatic mutation is necessary for early skin neoplasms is illustrated by Cockayne syndrome (and possibly patient 11961), where XP-like changes in the skin are not observed despite an enhanced u. v. mutability of cultured fibroblasts. Xeroderma pigmentosum, ataxia-telangiectasia and Cockayne syn\u00addrome all show progressive neurological disease, suggesting that common factors are involved in DNA repair and the normal development and function of the nervous system. Fibroblasts from certain Huntington\u2019s disease patients also show some sensitivity to ionizing radiation but this cannot at present be attributed to a DNA-repair deficiency. Patients with ataxia-telangiectasia also show a severely depressed immune response, and a search for other individuals with impaired im\u00admunity revealed patient 46BR, whose cells are sensitive to a wide range of DNA-damaging agents. It is suggested that common factors may be involved in DNA repair and the proper development and functioning of the immune system. One possibility is (by analogy with the recA mutation in bacteria) that common steps exist between some types of DNA repair and the somatic recombination events that are involved in the generation of immunoglobulin genes. Human DNA-repair-deficient mutants may not yet have proved their value in yielding an understanding of the molecular mechanisms of DNA repair, but they have shown that several unexpected aspects of human health may be linked to functional DNA-repair processes.<\/jats:p>","DOI":"10.1098\/rspb.1981.0038","type":"journal-article","created":{"date-parts":[[2006,12,18]],"date-time":"2006-12-18T18:11:28Z","timestamp":1166465488000},"page":"263-278","source":"Crossref","is-referenced-by-count":12,"title":["Some DNA-repair-deficient human syndromes and their implications for human health"],"prefix":"10.1098","volume":"212","author":[{"given":"B. A.","family":"Bridges","sequence":"first","affiliation":[{"name":"M. R. C. Cell Mutation Unit, University of Sussex, Falmer, Brighton BN1 9QG, U. K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","reference":[{"key":"p_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)90154-3"},{"key":"p_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(76)92652-0"},{"key":"p_3","unstructured":"A rlett C. F. 1980a Mutagenesis in repair-deficient hum an cell strains. In Progress in environmental mutagenesis (ed. M. Alacevic) pp. 161-174. A m sterdam : E Isevier\/N orth Holland."},{"key":"p_4","unstructured":"A rlett C. F. 19806 Presym ptom atic diagnosis of H untington's disease? i 540."},{"key":"p_5","first-page":"173","article-title":"A hum an subject with a new defect in repair of ultraviolet damage. invest","volume":"70","author":"Lehm","year":"1978","journal-title":"Derm."},{"key":"p_6","first-page":"276","article-title":"Radiosensitivity in H untington's chorea cell strains: a possible preclinical diagnosis","volume":"42","author":"Muriel W. J.","year":"1979","journal-title":"Heredity. Lond."},{"key":"p_7","first-page":"745","article-title":"Studies on a new case ol xeroderm a pigm entosum (XP3BR) from com - plem entation group G with cellular sensitivity to ionizing radiation","volume":"1","author":"Lehm","year":"1981","journal-title":"Carcinogenesis"},{"key":"p_8","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(78)90078-8"},{"key":"p_9","doi-asserted-by":"publisher","DOI":"10.1038\/283523a0"},{"key":"p_10","unstructured":"Bridges B. A. Strauss G. H . Hall-Sm ith P. & Price M. 1981 Induction of somatic m u ta - tions and im pairm ent of immune capacity by PUVA treatm en t and their relation to skin cancer in m an. In Psoralens in cosmetics and dermatology. New Y ork: Plenum Press. (In the press.)"},{"key":"p_11","unstructured":"Bridges B. A. & H arnden D. G. (eds) 1981 - cellular and molecular link between cancer neuropathology and immune deficiency. London: John Wiley. (In the press.)"},{"key":"p_12","doi-asserted-by":"publisher","DOI":"10.1038\/218652a0"},{"key":"p_13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.3.1422"},{"key":"p_14","first-page":"253","article-title":"Immunologic im plications of PUVA therapy in psoriasis vulgaris. J.invest","volume":"68","author":"Cormane R. H.","year":"1979","journal-title":"Derm."},{"key":"p_15","unstructured":"Cox R. 1981 A cellular description of the repair defect in ataxia-telangiectasia. In Ataxiatelangiectasia -a cellular and molecular link between cancer neuropathology and immune deficiency (ed. B. A. Bridges & D. G. H arnden). London: Jo h n Wiley. (In the press.)"},{"key":"p_16","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-197704000-00008"},{"key":"p_17","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(74)90022-1"},{"key":"p_18","unstructured":"Guzzetta F. 1972 Cockayne-Neill-Dingwall syndrome. In (ed. P. J. Vinken & E. W. Bruyn) pp. 431-440. A m sterdam : N orth Holland."},{"key":"p_19","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197308)32:2<380::AID-CNCR2820320214>3.0.CO;2-2"},{"key":"p_20","first-page":"685","article-title":"Bowenoid lesions, Bowen's disease and keratoacanthom as in long-term PU V A -treated patients. Br. J","volume":"101","author":"Hoffman C.","year":"1979","journal-title":"Derm."},{"key":"p_21","doi-asserted-by":"crossref","unstructured":"Inoue T. Hirano K. Yokiyama A. K ada T. & K ato H . 1977 DNA repair enzymes in ataxia-telangiectasia and Bloom's syndrome fibroblasts. Biochim. biophys. acta 479 497-500.","DOI":"10.1016\/0005-2787(77)90042-9"},{"key":"p_22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.2.919"},{"key":"p_23","doi-asserted-by":"crossref","unstructured":"Keijzer E. Jaspers N. G. J. A braham s P. J . Taylor A. M. R . A rlett C. F. Zelle B. Takebe H . K inm ont P. D. S. & Bootsm a D. 1979 A seventh com plem entation group in excision-deficient xeroderm a pigm entosum . M utation Res. 62 183-190.","DOI":"10.1016\/0027-5107(79)90231-8"},{"key":"p_24","unstructured":"Kidson C. & Dambergs R. 1981 Nervous system developm ent and ataxia-telangiectasia. In Ataxia-telangiectasia -a cellular and molecular link between cancer neuropathology and im m une deficiency (ed. B. A. Bridges & D. G. H arnden). London: Jo h n W iley. 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H. 1980 R adiosensitivity in H u n tin g to n 's disease: Im plications for pathogenesis and presym ptom atic diagnosis. Lancet i 9-11.","DOI":"10.1016\/S0140-6736(80)90550-4"},{"key":"p_37","doi-asserted-by":"publisher","DOI":"10.1038\/260444a0"},{"key":"p_38","doi-asserted-by":"crossref","unstructured":"Paterson M. C. Sm ith B. P . K night P. A. & Anderson A. K. 1977 A taxia-telangiectasia: an inherited hum an disease involving radio-sensitivity m alignancy and defective DNA repair. Research in photobiology (ed. A. Castellani) pp. 207-218. New Y ork: Plenum Press","DOI":"10.1007\/978-1-4613-4160-4_22"},{"key":"p_39","first-page":"70A","article-title":"Cytogenetic studies of ataxia-telangiectasia. A m . J . hum","volume":"26","author":"Bender M. A.","year":"1974","journal-title":"Genet."},{"key":"p_40","doi-asserted-by":"crossref","unstructured":"Reed W. B. 1976 T reatm ent of psoriasis w ith oral psoralens and longwave ultraviolet-light. 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