Aldehyde oxidase generates deoxyribonucleic acid single strand nicks in vitro

We purified aldehyde oxidase (AO) from rabbit livers and found that AO produced deoxyribonucleic acid (DNA) single strand nicks in vitro. Acetaldehyde, benzaldehyde, and certain purine bases were effective substrates for AO catalyzed DNA strand nicking. DNA strand nicking did not occur with the reducing substrates nicotinamide-adenine dinucleotide or dithionite that produce superoxide anion (O2'(-)). Inclusion of electron transport inhibitors, potassium cyanide, ferricyanide or menadione, prevented AO catalyzed nicking. AO induced DNA strand nicking was dependent upon hydrogen peroxide (H2O2) formation and most likely generation of hydroxyl radical (HO'). The present observations may be pertinent to the recently proposed involvement of AO in inherited juvenile familial amyotrophic lateral sclerosis (JFALS) and other oxygen radical mediated diseases.