Although alcohol consumption is related to increased cancer risk, its molecular 
mechanism remains unclear. Here, we demonstrate that an intake of 10% alcohol 
for 4 weeks in rats is genotoxic due to induction of micronuclei. Acetaldehyde 
(AA), the first product of ethanol metabolism, is believed to be responsible for 
DNA damage induced by alcohol. Here, we observe that AA effectively blocks DNA 
replication elongation in mammalian cells, resulting in DNA double-strand breaks 
associated with replication. AA-induced DNA damage sites colocalize with the 
homologous recombination (HR) repair protein RAD51. HR measured in the 
hypoxhantineguaninefosforibosyltransferase (HPRT) gene is effectively induced by 
AA and recombination defective mammalian cells are hypersensitive to AA, clearly 
demonstrating that HR is essential in the repair of AA-induced DNA damage. 
Altogether, our data indicate that alcohol genotoxicity related to AA produces 
replication lesions on DNA triggering HR repair.