Genotoxic lesions formed by formaldehyde and acetaldehyde. Formaldehyde reacts with the amine group on guanine, adenine, and cytosine to form N²-hydroxymethyl-guanine (N²-OHMe-dG), N⁶-hydroxymethyl-adenine (N⁶-OHMe-dA), and N⁴-hydroxymethyl-cytosine (N⁴-OHMe-dC), respectively. Acetaldehyde initially forms an unstable N²-ethylidene-guanine adduct, which spontaneously reacts with an additional acetaldehyde molecule to form the cyclic adduct N¹,N²-propano-guanine. Formaldehyde can form DNA interstrand cross-links through the formation of a methylene bridge that covalently links guanine, adenine, and cytosine on opposing DNA strands. Although only dG-dG, dA-dA, and dG-dC are shown, any combinations of dG, dA, and dC can be cross-linked by formaldehyde. Acetaldehyde reacts with opposing guanines to form cross-links that exist in equilibrium between 3 chemical states. Formaldehyde can also form methylene cross-links between guanine and the amino acids cysteine, histidine, tryptophan, and lysine to give rise to DNA-protein cross-links. The DNA repair pathways with activity toward the respective aldehyde-DNA lesions are shown.