The formation and measurement of DNA neuroadduction in alcoholism. Case report

We present a case report of an intoxicated alcoholic driver who sustained fatal motor vehicle injuries. We subsequently quantified ethanol-derived acetaldehyde (ACE) DNA products in his brain, which may represent a major contributor to clinical alcoholic use and complications. Further, ACE DNA neuroadducts may indicate chronic exposure to alcohol, as demonstrated by 32P-prelabeled DNA and two-dimensional thin-layer chromatography. ACE and other unknown neuroadducts were evident in the histologically normal frontal, parietal, and caudate lobes. DNA neuroadduct formation was extensive and similar in three separate brain regions with normal histology. Contributing neuroadduction by chronic drug abuse is also possible, though the deceased's terminal acute blood screens for recent drug abuse were negative. The mechanism of alcohol neurotoxicity remains unknown, but biochemical nonenzymatic changes of DNA at the nucleic acid level (adduct formation) can alter gene function and stability. DNA neuroadduct detection may represent an important determinant in quantifying neurotoxicity from drug abuse or alcoholism in the absence of history, the presence of negative blood, tissue, and urine assays for recent drug and alcohol use, and the absence of neuropathology.