Fructose triggers DNA modification and damage in an Escherichia coli plasmid

The nonenzymatic reaction between reducing sugars and amino groups of long- lived macromolecules results in an array of chemical modifications that may account for several physiological complications. The characteristics of th e reaction are directly related to the type of the reducing sugars involved , whether aldoses or ketoses, phosphorylated or non-phosphorylated, and the se in rum determine the consequences of the induced modifications. So far, most studies have been focused on the nonenzymatic reaction between glucose and proteins, while the reaction with fructose, a faster glycating agent, attracted only a minor attention. We have recently demonstrated that long-t erm fructose consumption induces age-related changes in collagen from skin and cortical bones faster than glucose. In the present study we provide evi dence that fructose and its phosphate metabolites can modify DNA faster tha n glucose and its phosphate metabolites under in vitro conditions. Incubati ng the plasmid pBR322 with fructose and glucose phosphate metabolites induc ed DNA modifications and damage that were verified by gel electrophoresis a nd transformation capacity of the plasmid into an Escherichia coil host. Th e intensity of the tested sugars to modified and damage DNA after incubatio n for 15 days increased significantly in the following order: glucose l-pho sphate < glucose < glucose 6-phosphate < fructose l-phosphate < fructose < fructose 6-phosphate. The data suggest that fructose should deserve more at tention as a factor that may influence glycation and induce physiological c omplications. <(c)> 2001 Elsevier Science Inc. All rights reserved.