OXIDATIVE DNA-DAMAGE INDUCED BY POTASSIUM BROMATE IN ISOLATED RAT RENAL PROXIMAL TUBULES AND RENAL NUCLEI

Oxidative damage caused by potassium bromate (KBrO3), a rat renal carc inogen, was investigated using in vitro preparations of rat renal prox imal tubules (RPT) and renal nuclear fractions. Release of lactate deh ydrogenase and decrease of SH-group content in RPT (1 mg protein/ml) b y KBrO3 (0.5-5 mM) in a concentration- and time-dependent manner were observed. Peroxidized arachidonic acid and 8-hydroxydeoxyguanosine (8- OH-dG) levels in RPT were increased after administration of 2 and 5 mM KBrO3. 8-OH-dG formation was observed after incubation of renal nucle i with a lipid-peroxiding system, autooxidized methyl linolenate, or K BrO3. These findings provide support for involvement of lipid peroxida tion in producing oxidized DNA damage by KBrO3 directly to RPT, the ta rget site for renal carcinogenesis.