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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1988 Jun;47(6):445–451. doi: 10.1136/ard.47.6.445

Increased sensitivity of lymphocytes from patients with systemic autoimmune diseases to DNA alkylation by the methylating carcinogen N-methyl-N-nitrosourea.

P D Lawley 1, R Topper 1, A M Denman 1, W Hylton 1, I D Hill 1, G Harris 1
PMCID: PMC1003543  PMID: 3382263

Abstract

Lymphocytes from patients with various diseases associated with autoimmunity showed both impaired capacity to repair O6-methylguanine (a powerful, promutagenic, directly miscoding base lesion) and increased sensitivity to the cytocidal effects of cellular methylation by N-methyl-N-nitrosourea (MNU) compared with normal controls and patients with other disorders. Defective repair of O6-methylguanine was significantly associated with arthritis and myositis in the group with systemic lupus erythematosus (SLE), and increased sensitivity to the toxic action of MNU was associated with the presence of immune complexes and the administration of steroids to patients with Behçet's syndrome. The results indicate that lymphocytes from patients with the autoimmune diseases studied are more susceptible to DNA damage with possible relevance to aetiopathogenesis.

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Selected References

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

  1. Burnet F. M. Intrinsic mutagenesis: a genetic basis of ageing. Pathology. 1974 Jan;6(1):1–11. doi: 10.3109/00313027409077150. [DOI] [PubMed] [Google Scholar]
  2. Cleaver J. E. DNA damage and repair in light-sensitive human skin disease. J Invest Dermatol. 1970 Mar;54(3):181–195. doi: 10.1111/1523-1747.ep12280225. [DOI] [PubMed] [Google Scholar]
  3. Diamond B., Scharff M. D. Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5841–5844. doi: 10.1073/pnas.81.18.5841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gerson S. L., Miller K., Berger N. A. O6 alkylguanine-DNA alkyltransferase activity in human myeloid cells. J Clin Invest. 1985 Dec;76(6):2106–2114. doi: 10.1172/JCI112215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Griffiths G. M., Berek C., Kaartinen M., Milstein C. Somatic mutation and the maturation of immune response to 2-phenyl oxazolone. Nature. 1984 Nov 15;312(5991):271–275. doi: 10.1038/312271a0. [DOI] [PubMed] [Google Scholar]
  6. Harris G., Lawley P. D., Asbery L. J., Chandler P. M., Jones M. G. Autoimmune haemolytic disease in mice after exposure to a methylating carcinogen. Immunology. 1983 Jul;49(3):439–449. [PMC free article] [PubMed] [Google Scholar]
  7. Jeggo P. Isolation and characterization of Escherichia coli K-12 mutants unable to induce the adaptive response to simple alkylating agents. J Bacteriol. 1979 Sep;139(3):783–791. doi: 10.1128/jb.139.3.783-791.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lawley P. D., Harris G., Phillips E., Irving W., Colaço C. B., Lydyard P. M., Roitt I. M. Repair of chemical carcinogen-induced damage in DNA of human lymphocytes and lymphoid cell lines--studies of the kinetics of removal of O6-methylguanine and 3-methyladenine. Chem Biol Interact. 1986 Jan;57(1):107–121. doi: 10.1016/0009-2797(86)90053-0. [DOI] [PubMed] [Google Scholar]
  9. Mason R. M., Barnes C. G. Behçet's syndrome with arthritis. Ann Rheum Dis. 1969 Mar;28(2):95–103. doi: 10.1136/ard.28.2.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  11. Theofilopoulos A. N., Prud'Homme G. J., Dixon F. J. Autoimmune aspects of systemic lupus erythematosus. Concepts Immunopathol. 1985;1:190–218. [PubMed] [Google Scholar]
  12. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]

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