Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Feb;79(2):653–656. doi: 10.1172/JCI112863

Increased single strand breaks in DNA of lymphocytes from diabetic subjects.

M Lorenzi, D F Montisano, S Toledo, H C Wong
PMCID: PMC424159  PMID: 3543058

Abstract

Certain aspects of the chronic complications of diabetes suggest that, with time, the abnormal metabolic milieu leads to irreversible changes in some cell populations. Since we have previously observed that high glucose concentrations induce an increase in single strand breaks in the DNA of cultured human endothelial cells, we have investigated whether the same abnormality occurs in cells derived from the in vivo diabetic environment. Peripheral blood lymphocytes obtained from 21 type I diabetic patients and age- and sex-matched controls were tested for rate of unwinding in alkali (a measure of DNA single strand breaks). The patients were subdivided into two groups on the basis of glycohemoglobin values above or below 9%. The group with glycohemoglobin values of 12.9 +/- 2.4% (mean +/- SD), but not the group with glycohemoglobin values of 7.4 +/- 1.5%, showed accelerated unwinding of lymphocyte DNA when compared to controls (P less than 0.01). These studies suggest that poorly controlled diabetes may result in DNA lesions, whose impact on long-term complications deserves to be investigated.

Full text

PDF
653

Selected References

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

  1. Birnboim H. C., Jevcak J. J. Fluorometric method for rapid detection of DNA strand breaks in human white blood cells produced by low doses of radiation. Cancer Res. 1981 May;41(5):1889–1892. [PubMed] [Google Scholar]
  2. Bodansky H. J., Wolf E., Cudworth A. G., Dean B. M., Nineham L. J., Bottazzo G. F., Matthews J. A., Kurtz A. B., Kohner E. M. Genetic and immunologic factors in microvascular disease in type I insulin-dependent diabetes. Diabetes. 1982 Jan;31(1):70–74. doi: 10.2337/diab.31.1.70. [DOI] [PubMed] [Google Scholar]
  3. Brody J. I., Merlie K. Metabolic and biosynthetic features of lymphocytes from patients with diabetes mellitus: similarities to lymphocytes in chronic lymphocytic leukaemia. Br J Haematol. 1970 Aug;19(2):193–201. doi: 10.1111/j.1365-2141.1970.tb01616.x. [DOI] [PubMed] [Google Scholar]
  4. Bucala R., Model P., Cerami A. Modification of DNA by reducing sugars: a possible mechanism for nucleic acid aging and age-related dysfunction in gene expression. Proc Natl Acad Sci U S A. 1984 Jan;81(1):105–109. doi: 10.1073/pnas.81.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Casey J. I., Heeter B. J., Klyshevich K. A. Impaired response of lymphocytes of diabetic subjects to antigen of Staphylococcus aureus. J Infect Dis. 1977 Oct;136(4):495–501. doi: 10.1093/infdis/136.4.495. [DOI] [PubMed] [Google Scholar]
  6. Cheung H. C., Almira E. C., Kansal P. C., Reddy W. J. A membrane abnormality in lymphocytes from diabetic subjects. Endocr Res Commun. 1980;7(3):145–156. doi: 10.3109/07435808009065968. [DOI] [PubMed] [Google Scholar]
  7. Glassman A. B., Lindsay J. H., Jr, Bennett C. E., Hodges E. R., Jr Effects of insulin on phytohemagglutinin-P, concanavalin-A, and pokeweed mitogen in diabetic and nondiabetic lymphocytes. Ann Clin Lab Sci. 1981 Jan-Feb;11(1):9–14. [PubMed] [Google Scholar]
  8. Jones R. L., Peterson C. M. Hematologic alterations in diabetes mellitus. Am J Med. 1981 Feb;70(2):339–352. doi: 10.1016/0002-9343(81)90771-3. [DOI] [PubMed] [Google Scholar]
  9. Kohner E. M., Henkind P. Correlation of fluorescein angiogram and retinal digest in diabetic retinopathy. Am J Ophthalmol. 1970 Mar;69(3):403–414. doi: 10.1016/0002-9394(70)92273-7. [DOI] [PubMed] [Google Scholar]
  10. Lauritzen T., Frost-Larsen K., Larsen H. W., Deckert T. Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy. Diabetes. 1985 Aug;34 (Suppl 3):74–79. doi: 10.2337/diab.34.3.s74. [DOI] [PubMed] [Google Scholar]
  11. Lorenzi M., Cagliero E., Toledo S. Glucose toxicity for human endothelial cells in culture. Delayed replication, disturbed cell cycle, and accelerated death. Diabetes. 1985 Jul;34(7):621–627. doi: 10.2337/diab.34.7.621. [DOI] [PubMed] [Google Scholar]
  12. Lorenzi M., Montisano D. F., Toledo S., Barrieux A. High glucose induces DNA damage in cultured human endothelial cells. J Clin Invest. 1986 Jan;77(1):322–325. doi: 10.1172/JCI112295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Price G. B., Modak S. P., Makinodan T. Age-associated changes in the DNA of mouse tissue. Science. 1971 Mar 5;171(3974):917–920. doi: 10.1126/science.171.3974.917. [DOI] [PubMed] [Google Scholar]
  14. Schimke R. T., Sherwood S. W., Hill A. B., Johnston R. N. Overreplication and recombination of DNA in higher eukaryotes: potential consequences and biological implications. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2157–2161. doi: 10.1073/pnas.83.7.2157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Schraufstatter I. U., Hinshaw D. B., Hyslop P. A., Spragg R. G., Cochrane C. G. Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide. J Clin Invest. 1986 Apr;77(4):1312–1320. doi: 10.1172/JCI112436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Seto S., Carrera C. J., Kubota M., Wasson D. B., Carson D. A. Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes. J Clin Invest. 1985 Feb;75(2):377–383. doi: 10.1172/JCI111710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shmookler Reis R. J., Lumpkin C. K., Jr, McGill J. R., Riabowol K. T., Goldstein S. Extrachromosomal circular copies of an 'inter-Alu' unstable sequence in human DNA are amplified during in vitro and in vivo ageing. Nature. 1983 Feb 3;301(5899):394–398. doi: 10.1038/301394a0. [DOI] [PubMed] [Google Scholar]
  18. Singh N., Poirier G., Cerutti P. Tumor promoter phorbol-12-myristate-13-acetate induces poly ADP-ribosylation in human monocytes. Biochem Biophys Res Commun. 1985 Feb 15;126(3):1208–1214. doi: 10.1016/0006-291x(85)90314-6. [DOI] [PubMed] [Google Scholar]
  19. Staiano-Coico L., Darzynkiewicz Z., Hefton J. M., Dutkowski R., Darlington G. J., Weksler M. E. Increased sensitivity of lymphocytes from people over 65 to cell cycle arrest and chromosomal damage. Science. 1983 Mar 18;219(4590):1335–1337. doi: 10.1126/science.6828861. [DOI] [PubMed] [Google Scholar]
  20. Staiano-Coico L., Darzynkiewicz Z., Hefton J. M., Dutkowski R., Darlington G. J., Weksler M. E. Increased sensitivity of lymphocytes from people over 65 to cell cycle arrest and chromosomal damage. Science. 1983 Mar 18;219(4590):1335–1337. doi: 10.1126/science.6828861. [DOI] [PubMed] [Google Scholar]
  21. Stark G. R., Wahl G. M. Gene amplification. Annu Rev Biochem. 1984;53:447–491. doi: 10.1146/annurev.bi.53.070184.002311. [DOI] [PubMed] [Google Scholar]
  22. Tilton R. G., Faller A. M., Burkhardt J. K., Hoffmann P. L., Kilo C., Williamson J. R. Pericyte degeneration and acellular capillaries are increased in the feet of human diabetic patients. Diabetologia. 1985 Dec;28(12):895–900. doi: 10.1007/BF00703132. [DOI] [PubMed] [Google Scholar]
  23. Viberti G. C., Bilous R. W., Mackintosh D., Bending J. J., Keen H. Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes. Br Med J (Clin Res Ed) 1983 Feb 19;286(6365):598–602. doi: 10.1136/bmj.286.6365.598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vracko R., Benditt E. P. Restricted replicative life-span of diabetic fibroblasts in vitro: its relation to microangiopathy. Fed Proc. 1975 Jan;34(1):68–70. [PubMed] [Google Scholar]
  25. Watson W. A., Petrie J. C., Galloway D. B., Bullock I., Gilbert J. C. In vivo cytogenetic activity of sulphonylurea drugs in man. Mutat Res. 1976 Feb;38(1):71–80. doi: 10.1016/0165-1161(76)90080-7. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES