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J Clin Invest. 1986 January; 77(1): 322–325.
PMCID: PMC423344

High glucose induces DNA damage in cultured human endothelial cells.


Morphologic and functional abnormalities of vascular endothelium are well recognized in diabetes. In view of our previous finding that high glucose concentrations accelerate death and hamper replication of cultured human endothelial cells, we have investigated in the same model the possibility that exposure to high glucose may result in DNA damage. DNA from human endothelial cells--but not from fibroblasts--exposed to 30 mM glucose for 9-14 d manifested an accelerated rate of unwinding in alkali indicative of an increased number of single strand breaks (P less than 0.001 vs. control). Endothelial cells exposed to high glucose also manifested an increased amount of hydroxy-urea-resistant thymidine incorporation (333 +/- 153 cpm/10(5) cells vs. 88 +/- 42 in control cells, mean +/- SD, P = 0.04), which is indicative of increased DNA repair synthesis. Neither DNA damage nor repair synthesis were increased by medium hypertonicity achieved with 30 mM mannitol. These findings suggest the possibility that, under conditions of high ambient glucose, excess glucose entry in cells that are insulin independent for glucose transport may, directly or indirectly, perturb DNA function. Further, they suggest the possibility that different individual capabilities to repair DNA damage--a process that is under genetic control--may represent a mechanism for different individual susceptibilities to development of diabetic vascular complication.

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Selected References

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  • Dolgov VV, Zaikina OE, Bondarenko MF, Repin VS. Aortic endothelium of alloxan diabetic rabbits: a quantitative study using scanning electron microscopy. Diabetologia. 1982 May;22(5):338–343. [PubMed]
  • Parving HH. Increased microvascular permeability to plasma proteins in short- and long-term juvenile diabetics. Diabetes. 1976;25(2 Suppl):884–889. [PubMed]
  • Parthasarathy N, Spiro RG. Effect of diabetes on the glycosaminoglycan component of the human glomerular basement membrane. Diabetes. 1982 Aug;31(8 Pt 1):738–741. [PubMed]
  • West KM, Erdreich LJ, Stober JA. A detailed study of risk factors for retinopathy and nephropathy in diabetes. Diabetes. 1980 Jul;29(7):501–508. [PubMed]
  • Ganda OP. Pathogenesis of macrovascular disease in the human diabetic. Diabetes. 1980 Nov;29(11):931–942. [PubMed]
  • Corkey RF, Corkey BE, Gimbrone MA., Jr Hexose transport in normal and SV40-transformed human endothelial cells in culture. J Cell Physiol. 1981 Mar;106(3):425–434. [PubMed]
  • Betz AL, Bowman PD, Goldstein GW. Hexose transport in microvascular endothelial cells cultured from bovine retina. Exp Eye Res. 1983 Feb;36(2):269–277. [PubMed]
  • Stevens VJ, Vlassara H, Abati A, Cerami A. Nonenzymatic glycosylation of hemoglobin. J Biol Chem. 1977 May 10;252(9):2998–3002. [PubMed]
  • Clements RS., Jr Diabetic neuropathy--new concepts of its etiology. Diabetes. 1979 Jun;28(6):604–611. [PubMed]
  • 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. [PubMed]
  • Morita J, Ueda K, Nanjo S, Komano T. Sequence specific damage of DNA induced by reducing sugars. Nucleic Acids Res. 1985 Jan 25;13(2):449–458. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Birnboim HC, Jevcak JJ. 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]
  • 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. [PubMed]
  • Seto S, Carrera CJ, Kubota M, Wasson DB, Carson DA. Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes. J Clin Invest. 1985 Feb;75(2):377–383. [PMC free article] [PubMed]
  • Sheridan RB, 3rd, Huang PC. Single strand breakage and repair in eukaryotic DNA as assayed by S1 nuclease. Nucleic Acids Res. 1977 Feb;4(2):299–318. [PMC free article] [PubMed]
  • Brandt WN, Flamm WG, Bernheim NJ. The value of hydroxyurea in assessing repair synthesis of DNA in HeLa cells. Chem Biol Interact. 1972 Oct;5(5):327–339. [PubMed]
  • Lindberg U, Skoog L. A method for the determination of dATP and dTTP in picomole amounts. Anal Biochem. 1970 Mar;34:152–160. [PubMed]
  • Kohn KW, Friedman CA, Ewig RA, Iqbal ZM. DNA chain growth during replication of asynchronous L1210 cells. Alkaline elution of large DNA segments from cells lysed on filters. Biochemistry. 1974 Sep 24;13(20):4134–4139. [PubMed]
  • Howard BV, Mott DM, Fields RM, Bennett PH. Insulin stimulation of glucose entry in cultured human fibroblasts. J Cell Physiol. 1979 Oct;101(1):129–138. [PubMed]
  • Berhanu P, Olefsky JM. Effects of insulin and insulin-like agents on the glucose transport system of cultured human fibroblasts. Diabetes. 1981 Jun;30(6):523–529. [PubMed]
  • Turner JL, Bierman EL. Effects of glucose and sorbitol on proliferation of cultured human skin fibroblasts and arterial smooth-muscle cells. Diabetes. 1978 May;27(5):583–588. [PubMed]
  • Mills JL, Baker L, Goldman AS. Malformations in infants of diabetic mothers occur before the seventh gestational week. Implications for treatment. Diabetes. 1979 Apr;28(4):292–293. [PubMed]
  • Chazan BI, Balodimos MC, Ryan JR, Marble A. Twenty-five to forty-five years of diabetes with and without vascular complications. Diabetologia. 1970 Dec;6(6):565–569. [PubMed]
  • Dornan TL, Ting A, McPherson CK, Peckar CO, Mann JI, Turner RC, Morris PJ. Genetic susceptibility to the development of retinopathy in insulin-dependent diabetics. Diabetes. 1982 Mar;31(3):226–231. [PubMed]

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