New DNA adducts of crotonaldehyde and acetaldehyde.
This paper summarizes our recent studies on adducts produced in the reactions of the carcinogens crotonaldehyde (2-butenal) and acetaldehyde with deoxyguanosine (dG) and DNA. Human exposure to these carcinogens can be considerable, from both exogenous and endogenous sources. Crotonaldehyde reacts with DNA to form Michael addition products, a pathway that has been well described. We describe a second major pathway, in which 3-hydroxybutanal, formed by addition of H(2)O to crotonaldehyde, reacts with DNA to produce the Schiff base N(2)-(3-hydroxybut-1-ylidene)dG as well as several diastereomers of N(2)-paraldol-dG. Acetaldehyde reacts with DNA and dG giving a major Schiff base adduct, N(2)-ethylidene-dG. A cross-linked adduct of acetaldehyde has been characterized for the first time, and other adducts resulting from the reaction of two and three molecules of acetaldehyde with dG have been observed. The results of these studies demonstrate that some structurally unique adducts are formed from these carcinogenic aldehydes and suggest some new directions for research on the potential role of aldehydes in human cancer.
Hecht
S S
SS
University of Minnesota Cancer Center, Box 806, Mayo, 420 Delaware Street S.E., Minneapolis, MN 55455, USA. hecht002@gold.tc.umn.edu
McIntee
E J
EJ
Wang
M
M
D000079:Acetaldehyde; D000447:Aldehydes / Q000737:chemistry*; D002273:Carcinogens / Q000737:chemistry*; D055598:Chemical Phenomena; D002621:Chemistry; D018736:DNA Adducts / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced
D000447:Aldehydes; D002273:Carcinogens; D018736:DNA Adducts; C012796:2-butenal; D003849:Deoxyguanosine; D000079:Acetaldehyde