Fructose and related phosphate derivatives impose DNA damage and apoptosis in L5178Y mouse lymphoma cells

Glycation 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 consequences of the reaction are directly related to the reactivity of the sugars involved, whether aldoses or ketoses, phosphorylated or non-phosphorylated. So far, most studies have been focused on glucose, while fructose, a faster glycating agent, attracted minor attention. We have recently demonstrated that under in vitro conditions fructose and its phosphate derivatives can modify plasmid DNA faster than glucose and its phosphate metabolites. In the present study we provide further evidences suggesting that fructose and its phosphate metabolites, at the tested conditions, are cytotoxic and inflict deleterious DNA modifications to L5178Y cells in culture. Damage was verified by viable cell counts, MTT assay, colony forming ability, induction of mutation in the thymidine kinase gene, internucleosomal DNA cleavage, and single strand breaks. The intensity of the tested sugars to impose damage increased significantly in the following order: sucrose = glucose 1-phosphate < glucose < glucose 6-phosphate < fructose 1-phosphate = fructose < fructose 6-phosphate. Aminoguanidine, an inhibitor of the glycation reaction, inhibited internucleosomal DNA cleavage. Taken together, these results suggest that fructose triggers deleterious modification in cultured cells through the glycation process, and thus should deserve more attention as an agent that may induce physiological complications.