Genotoxicity of advanced glycation end products in mammalian cells

Cancer Lett. 2003 Feb 20;190(2):151-6. doi: 10.1016/s0304-3835(02)00626-2.

Abstract

In patients with chronic renal failure, cancer incidence is enhanced. Since levels of advanced glycation end products (AGEs) are markedly elevated in renal insufficiency, we investigated potential effects of various AGEs on structural DNA integrity in tubule cells. The comet-assay was employed, a method based on the computer-aided microscopic analysis of single cells after electrophoretic separation of their nuclear DNA. Incubation of pig kidney LLC-PK1-cells for 24 h with AGE-BSA (AGE-bovine serum albumin), carboxymethyllysine-BSA as well as methylglyoxal-BSA resulted in a significant increase in DNA damage. Pretreatment of the cells with the proteases trypsin and bromelain abolished the AGE-induced comet-formation. This is in agreement with the idea that the observed genotoxicity of AGEs could be receptor-mediated and that proteases inactivate the extracellular domain of the receptor for AGEs. Binding of AGEs to the RAGE receptor leads to an increased intracellular formation of active oxygen species, which are known to induce DNA damage. It is concluded that AGEs induce genotoxicity in tubule cells, which may be involved in the enhanced cancer development in advanced kidney diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Comet Assay
  • DNA Damage / drug effects*
  • Glycation End Products, Advanced / metabolism
  • Glycation End Products, Advanced / toxicity*
  • Humans
  • Kidney Diseases / chemically induced
  • Kidney Diseases / complications
  • Kidney Diseases / genetics
  • Kidney Neoplasms / chemically induced
  • Kidney Neoplasms / complications
  • Kidney Neoplasms / genetics
  • Serum Albumin, Bovine / metabolism
  • Serum Albumin, Bovine / pharmacology
  • Swine

Substances

  • Glycation End Products, Advanced
  • Serum Albumin, Bovine