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 carcinogen, was investigated using in vitro preparations of rat renal proximal tubules (RPT) and renal nuclear fractions. Release of lactate dehydrogenase and decrease of SH-group content in RPT (1 mg protein/ml) by 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 nuclei with a lipid-peroxiding system, autooxidized methyl linolenate, or KBrO3. These findings provide support for involvement of lipid peroxidation in producing oxidized DNA damage by KBrO3 directly to RPT, the target site for renal carcinogenesis.
Sai
K
K
Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.
Tyson
C A
CA
Thomas
D W
DW
Dabbs
J E
JE
Hasegawa
R
R
Kurokawa
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001959:Bromates / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000187:drug effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000648:ultrastructure; D007680:Kidney Neoplasms / Q000139:chemically induced; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D001959:Bromates; D002273:Carcinogens; D017392:Thiobarbituric Acid Reactive Substances; C019536:potassium bromate; D016718:Arachidonic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007770:L-Lactate Dehydrogenase; D003849:Deoxyguanosine