Summary
In order to evaluate whether base modifications, apurinic/apyrimidinic site formation, strand breaks, or a combination of these lesions results from the interaction of glycation products with DNA, plasmid DNA was first reacted with these products, and then subjected to digestion with endonuclease III and endonuclease IV of Escherichia coli. Analysis of the differential effects of digestions with these enzymes by electrophoresis on agarose gels demonstrated that reactive glycation products produce both base modification and apurinic/apyrimidinic sites in DNA, in addition to the strand breaks observed after incubation with glycation products alone. These types of DNA damage may occur in specific diabetic cells where elevated levels of glycating sugars are associated with pathologic dysfunction.
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References
Lee AT, Cerami A (1987) Elevated glucose 6-phosphate levels are associated with plasmid mutations in vivo. Proc Natl Acad Sci USA 84: 8311–8314
Bucala R, Model P, Cerami A (1984) Modification of DNA by reducing sugars: a possible mechanism for nucleic acid aging and age-related dysfunction in gene expression. Proc Natl Acad Sci USA 81: 105–109
Bucala R, Model P, Russel M, Cerami A (1985) Modification of DNA by glucose 6-phosphate induces DNA rearrangements in an Escherichia coli plasmid. Proc Natl Acad Sci USA 82: 8439–8442
Lee AT, Cerami A (1987) The formation of reactive intermediate(s) of glucose 6-phosphate and lysine capable of reacting with DNA. Mutation Res 179: 151–158
Kelly SB, Olerud JE, Witztum JL, Curtiss LK, Gown AM, Odland GF (1989) A method for localizing the early products of nonenzymatic glycosylation in fixed tissue. J Invest Dermatol 73: 327–331
Brownlee M (1990) Advanced products of nonenzymatic glycosylation and the pathogenesis of diabetic complications. In: Rifkin H, Porte E (eds) Diabetes mellitus, theory and practice. Elsevier, New York, pp 279–291
Bunn HF, Higgins PJ (1981) Reaction of monosacharides with proteins: possible evolutionary significance. Science 213: 222–224
Levin JD, Johnson AW, Demple B (1988) Homogeneous Escherichia coli endonuclease IV. Characterization of an enzyme that recognizes oxidative damage in DNA. J Biol Chem 263: 8066–8071
Kochetkov NK, Budovskii El, Sverdlov ED, Simukova NA, Turchinskii MF, Shibaev VN (1972) Hydrolysis of N-glycosidic bonds in nucleosides, nucleotides, and their derivatives. In: Kotchekov NK, Budovskii El (eds) Organic chemistry of nucleic acids. Plenum, New York, pp 425–448
Loeb LA, Preston BD (1986) Mutagenesis by apurinic/apyrimidinic sites. Ann Rev Genet 20: 201–230
Hevesi L, Wolfson-Davidson E, Nagyn JB, Nagy OB, Bruylants A (1972) Contribution to the mechanism of the acidcatalyzed hydrolysis of purine nucleosides. J Am Chem Soc 94: 4715–4720
Zoltewicz JA, Clark DF (1972) Kinetics and mechanism of the hydrolysis of guanosine and 7-methylguanosine nucleosides in perchloric acid. J Org Chem 37: 1193–1197
Roy S, Sala R, Cagliero E, Lorenzi M (1990) Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci USA 87: 404–408
Angel P, Poting A, Malick U, Rahmsdorf AJ, Schorpp MH, Herrlich P (1986) Induction of metallothionein and other mRNA species by carcinogens and tumor promoters in primary human skin fibroblasts. Mol Cell Biol 6: 1760–1766
Rahmsdorf HJ, Mallik U, Ponta H, Herrlich P (1982) A B lymphocyte-specific high-turnover protein: constitutive expression in resting B cells and induction of synthesis in proliferating cells. Cell 29: 459–468
Valerie K, Delers A, Bruck C et al. (1988) Activation of human immunodeficiency virus type 1 by DNA damage in human cells. Nature 333: 78–81
Stein B, Rahmsdorf HJ, Steffen A, Litfin M, Herrlich P (1989) UV-induced DNA damage is an intermediate step in UV-induced expression of human immunodeficiency virus type 1, collagenase, c-fos, and metallothionein. Mol Cell Biol 9: 5169–5181
Okamoto H (1990) The molecular basis of experimental diabetes. In: Okamoto H (ed) Molecular biology of the islets of Langerhans. Cambridge University Press, Cambridge, pp 209–231
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Mullokandov, E.A., Franklin, W.A. & Brownlee, M. DNA damage by the glycation products of glyceraldehyde 3-phosphate and lysine. Diabetologia 37, 145–149 (1994). https://doi.org/10.1007/s001250050085
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DOI: https://doi.org/10.1007/s001250050085