New DNA adducts of crotonaldehyde and acetaldehyde

This paper summarizes our recent studies on adducts produced in the reactio ns of the carcinogens crotonaldehyde (2-butenal) and acetaldehyde with deox yguanosine (dG) and DNA. Human exposure to these carcinogens can be conside rable, from both exogenous and endogenous sources. Crotonaldehyde reacts wi th DNA to form Michael addition products, a pathway that has been well desc ribed. We describe a second major pathway, in which 3-hydroxybutanal, forme d by addition of H2O to crotonaldehyde, reacts with DNA to produce the Schi ff base N-2-(3-hydroxbut-1-ylidene)dG as well as several diastercomers of N -2-paraldol-dG. Acetaldehyde reacts with DNA and dG giving a major Schiff b ase adduc, N-2-ethylidene-dG. A cross-linked adduct of acetadehyde has been characterized for the first time, and other adducts resulting from the rea ction of two and three molecules of acetaldehyde with dG have been observed . The results of these studies demonstrate that some structurally unique ad ducts are formed from these carcinogenic aldehydes and suggest some new dir ections for research on the potential role of aldehydes in human cancer. (C ) 2001 Elsevier Science Ireland Ltd. All rights reserved.