Increased oxidative DNA products in patients with acute promyelocytic leukemia during arsenic therapy

Abstract

Arsenic trioxide (ATO) has been used to treat acute promyelocytic leukemia (APL), but the oxidative DNA damage occurring in patients has not been fully elucidated. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), one of the most abundant oxidative products of DNA, by enzyme-linked immunoassay, and reactive oxidative species (ROS), by luminol- and luminol-H2O2 chemiluminescence, in the plasma of four APL patients treated with ATO. After six courses of ATO therapy, the plasma 8-OHdG concentration had increased from 45.6+/-22.8 ng/mL to 310.2+/-239.6 ng/mL. The plasma chemiluminescence level did not change significantly. These findings suggest that ATO generates intracellular oxidative DNA damage, but this is not correlated with the plasma ROS level. The clinical significance of 8-OHdG during and after ATO therapy warrants further study.