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. 1990 Jan;85(1):135–138. doi: 10.1172/JCI114403

Carrier detection in xeroderma pigmentosum.

R Parshad 1, K K Sanford 1, K H Kraemer 1, G M Jones 1, R E Tarone 1
PMCID: PMC296397  PMID: 2295692

Abstract

We were able to detect clinically normal carriers of xeroderma pigmentosum (XP) genes with coded samples of either peripheral blood lymphocytes or skin fibroblasts, using a cytogenetic assay shown previously to detect individuals with cancer-prone genetic disorders. Metaphase cells of phytohemagglutinin-stimulated T-lymphocytes from eight individuals who are obligate heterozygotes for XP were compared with those from nine normal controls at 1.3, 2.3, and 3.3 h after x-irradiation (58 R) during the G2 phase of the cell cycle. Lymphocytes from the XP heterozygotes had twofold higher frequencies of chromatid breaks or chromatid gaps than normal (P less than 10(-5)) when fixed at 2.3 or 3.3 h after irradiation. Lymphocytes from six XP homozygotes had frequencies of breaks and gaps threefold higher than normal. Skin fibroblasts from an additional obligate XP heterozygote, when fixed approximately 2 h after x-irradiation (68 R), had a twofold higher frequency of chromatid breaks and a fourfold higher frequency of gaps than fibroblasts from a normal control. This frequency of aberrations in cells from the XP heterozygote was approximately half that observed in the XP homozygote. The elevated frequencies of chromatid breaks and gaps after G2 phase x-irradiation may provide the basis of a test for identifying carriers of the XP gene(s) within known XP families.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bootsma D., Mulder M. P., Cohen J. A., Pot F. Different inherited levels of DNA repair replication in xeroderma pigmentosum cell strains after exposure to ultraviolet irradiation. Mutat Res. 1970 May;9(5):507–516. doi: 10.1016/0027-5107(70)90035-7. [DOI] [PubMed] [Google Scholar]
  2. Chan G. L., Little J. B. Cross-sensitivity of certain xeroderma pigmentosum and Cockayne syndrome fibroblast strains to both ionizing radiation and ultraviolet light. Mol Gen Genet. 1981;181(4):562–563. doi: 10.1007/BF00428755. [DOI] [PubMed] [Google Scholar]
  3. Cleaver J. E., Bootsma D. Xeroderma pigmentosum: biochemical and genetic characteristics. Annu Rev Genet. 1975;9:19–38. doi: 10.1146/annurev.ge.09.120175.000315. [DOI] [PubMed] [Google Scholar]
  4. Cleaver J. E. Xeroderma pigmentosum: variants with normal DNA repair and normal sensitivity to ultraviolet light. J Invest Dermatol. 1972 Mar;58(3):124–128. doi: 10.1111/1523-1747.ep12538913. [DOI] [PubMed] [Google Scholar]
  5. Day R. S., 3rd Studies on repair of adenovirus 2 by human fibroblasts using normal, xeroderma pigmentosum, and xeroderma pigmentosum heterozygous strains. Cancer Res. 1974 Aug;34(8):1965–1970. [PubMed] [Google Scholar]
  6. Giannelli F., Pawsey S. A. DNA repair synthesis in human heterokaryons. II. A test for heterozygosity in xeroderma pigmentosum and some insight into the structure of the defective enzyme. J Cell Sci. 1974 Jun;15(1):163–176. doi: 10.1242/jcs.15.1.163. [DOI] [PubMed] [Google Scholar]
  7. Goth-Goldstein R. Repair of DNA damaged by alkylating carcinogens is defective in xeroderma pigmentosum-derived fibroblasts. Nature. 1977 May 5;267(5606):81–82. doi: 10.1038/267081a0. [DOI] [PubMed] [Google Scholar]
  8. Kleijer W. J., de Weerd-Kastelein E. A., Sluyter M. L., Keijzer W., de Wit J., Bootsma D. UV-induced DNA repair synthesis in cells of patients with different forms of xeroderma pigmentosum and of heterozygotes. Mutat Res. 1973 Dec;20(3):417–428. doi: 10.1016/0027-5107(73)90062-6. [DOI] [PubMed] [Google Scholar]
  9. Kraemer K. H., Slor H. Xeroderma pigmentosum. Clin Dermatol. 1985 Jan-Mar;3(1):33–69. doi: 10.1016/0738-081x(85)90096-3. [DOI] [PubMed] [Google Scholar]
  10. MOORHEAD P. S., NOWELL P. C., MELLMAN W. J., BATTIPS D. M., HUNGERFORD D. A. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res. 1960 Sep;20:613–616. doi: 10.1016/0014-4827(60)90138-5. [DOI] [PubMed] [Google Scholar]
  11. McCurry L. S., Jacobson M. K. Poly(ADP-ribose) synthesis following DNA damage in cells heterozygous or homozygous for the xeroderma pigmentosum genotype. J Biol Chem. 1981 Jan 25;256(2):551–553. [PubMed] [Google Scholar]
  12. Miskin R., Ben-Ishai R. Induction of plasminogen activator by UV light in normal and xeroderma pigmentosum fibroblasts. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6236–6240. doi: 10.1073/pnas.78.10.6236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Parshad R., Gantt R., Sanford K. K., Jones G. M. Chromosomal radiosensitivity of human tumor cells during the G2 cell cycle period. Cancer Res. 1984 Dec;44(12 Pt 1):5577–5582. [PubMed] [Google Scholar]
  14. Parshad R., Sanford K. K., Jones G. M. Chromatid damage after G2 phase x-irradiation of cells from cancer-prone individuals implicates deficiency in DNA repair. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5612–5616. doi: 10.1073/pnas.80.18.5612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Parshad R., Sanford K. K., Jones G. M. Chromosomal radiosensitivity during the G2 cell-cycle period of skin fibroblasts from individuals with familial cancer. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5400–5403. doi: 10.1073/pnas.82.16.5400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Parshad R., Sanford K. K., Jones G. M., Tarone R. E. G2 chromosomal radiosensitivity of ataxia-telangiectasia heterozygotes. Cancer Genet Cytogenet. 1985 Jan 1;14(1-2):163–168. doi: 10.1016/0165-4608(85)90227-4. [DOI] [PubMed] [Google Scholar]
  17. Pawsey S. A., Magnus I. A., Ramsay C. A., Benson P. F., Giannelli F. Clinical, genetic and DNA repair studies on a consecutive series of patients with xeroderma pigmentosum. Q J Med. 1979 Apr;48(190):179–210. [PubMed] [Google Scholar]
  18. Rainbow A. J. Reduced capacity to repair irradiated adenovirus in fibroblasts from xeroderma pigmentosum heterozygotes. Cancer Res. 1980 Nov;40(11):3945–3949. [PubMed] [Google Scholar]
  19. Ritter M. A., Williams J. R. Fluorescent-light-induced lethality and DNA repair in normal and xeroderma pigmentosum fibroblasts. Biochim Biophys Acta. 1981 Aug 27;655(1):18–25. doi: 10.1016/0005-2787(81)90061-7. [DOI] [PubMed] [Google Scholar]
  20. Sanford K. K., Parshad R., Gantt R., Tarone R. E., Jones G. M., Price F. M. Factors affecting and significance of G2 chromatin radiosensitivity in predisposition to cancer. Int J Radiat Biol. 1989 Jun;55(6):963–981. doi: 10.1080/09553008914551001. [DOI] [PubMed] [Google Scholar]
  21. Selsky C. A., Greer S. Host-cell reactivation of UV-irradiated and chemically-treated herpes simplex virus-1 by xeroderma pigmentosum, XP heterozygotes and normal skin fibroblasts. Mutat Res. 1978 Jun;50(3):395–405. doi: 10.1016/0027-5107(78)90044-1. [DOI] [PubMed] [Google Scholar]
  22. Setlow R. B., Faulcon F. M., Regan J. D. Defective repair of gamma-ray induced DNA damage in xeroderma pigmentosum cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1976 Feb;29(2):125–136. doi: 10.1080/09553007614550141. [DOI] [PubMed] [Google Scholar]
  23. Shiloh Y., Parshad R., Sanford K. K., Jones G. M. Carrier detection in ataxia-telangiectasia. Lancet. 1986 Mar 22;1(8482):689–690. doi: 10.1016/s0140-6736(86)91773-3. [DOI] [PubMed] [Google Scholar]
  24. Squires S., Johnson R. T. Kinetic analysis of UV-induced incision discriminates between fibroblasts from different xeroderma pigmentosum complementation groups, XPA heterozygotes and normal individuals. Mutat Res. 1988 Mar;193(2):181–192. doi: 10.1016/0167-8817(88)90048-x. [DOI] [PubMed] [Google Scholar]
  25. Swift M., Chase C. Cancer in families with xeroderma pigmentosum. J Natl Cancer Inst. 1979 Jun;62(6):1415–1421. [PubMed] [Google Scholar]
  26. Welshimer K., Swift M. Congenital malformations and developmental disabilities in ataxia-telangiectasia, Fanconi anemia, and xeroderma pigmentosum families. Am J Hum Genet. 1982 Sep;34(5):781–793. [PMC free article] [PubMed] [Google Scholar]

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