TOBACCO-SMOKE IS A SOURCE OF TOXIC REACTIVE GLYCATION PRODUCTS

Smokers have a significantly higher risk for developing coronary and c erebrovascular disease than nonsmokers. Advanced glycation end product s (AGEs) are reactive, cross-linking moieties that form from the react ion of reducing sugars and (he amino groups of proteins, lipids, and n ucleic acids. AGEs circulate in high concentrations in the plasma of p atients with diabetes or renal insufficiency and have been linked to t he accelerated vasculopathy seen in patients with these diseases. Beca use the curing of tobacco takes place under conditions that could lead to the formation of glycation products, we examined whether tobacco a nd tobacco smoke could generate these reactive species that would incr ease AGE formation in vivo. Our findings show that reactive glycation products are present in aqueous extracts of tobacco and in tobacco smo ke in a form that can rapidly react with proteins to form AGEs. This r eaction can be inhibited by aminoguanidine, a known inhibitor of AGE f ormation. We have named these glycation products ''glycotoxins.'' Like other known reducing sugars and reactive glycation products, glycotox ins form smoke, react with protein, exhibit a specific fluorescence wh en cross-linked to proteins, and are mutagenic. Glycotoxins are transf erred to the serum proteins of human smokers. AGE-apolipoprotein B and serum AGE levels in cigarette smokers were significantly higher than those in nonsmokers. These results suggest that increased glycotoxin e xposure may contribute to the increased incidence of atherosclerosis a nd high prevalence of cancer in smokers.