Acetaldehyde forms covalent GG intrastrand crosslinks in DNA

Carcinogens often generate mutable DNA lesions that contribute to cancer and aging. However, the chemical structure of tumorigenic DNA lesions formed by acetaldehyde remains unknown, although it has long been considered an environmental mutagen in alcohol, tobacco, and food. Here, we identify an aldehyde-induced DNA lesion, forming an intrastrand crosslink between adjacent guanine bases, but not in single guanine bases or in other combinations of nucleotides. The GG intrastrand crosslink exists in equilibrium in the presence of aldehyde, and therefore it has not been detected or analyzed in the previous investigations. The newly identified GG intrastrand crosslinks might explain the toxicity and mutagenicity of acetaldehyde in DNA metabolism.