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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.