HYPOCHLOROUS ACID-INDUCED BASE MODIFICATIONS IN ISOLATED CALF THYMUS DNA

Exposure of calf thymus DNA to hypochlorous acid/hypochlorite leads to extensive DNA base modification. Large concentration-dependent increa ses in pyrimidine oxidation products [thymine glycol (cis/trans), 5-hy droxycytosine, 5-hydroxyuracil, 5-hydroxyhydantoin] but not purine oxi dation products (8-hydroxyguanine, 2- and 8-hydroxyadenine, FAPy guani ne, FAPy adenine) were observed at pH 7.4. In addition, large increase s in 5-chlorouracil (probably formed from 5-chlorocytosine during samp le preparation), a novel chlorinated base, were observed. Addition of HOCl to DNA already damaged by (OH)-O-. generated by a mixture of asco rbate, copper(II) chloride, and hydrogen peroxide showed that hypochlo rous acid led to a loss of 8-hydroxyguanine, 2- and 8-hydroxyadenine, FAPy guanine, FAPy adenine, and 5-hydroxycytosine in a concentration-a nd pH-dependent manner. Nevertheless, time course studies suggested th at the formation of purine oxidation products in isolated DNA by hypoc hlorous acid was not a major oxidation pathway. If this pattern of dam age, especially the production of 5-chlorocytosine, is unique to hypoc hlorous acid, it might act as a ''fingerprint'' of damage to DNA by HO Cl.