A possible role for oxidative stress in potassium bromate (KBrO3) carcinogenesis. 1995

T Umemura, and K Sai, and A Takagi, and R Hasegawa, and Y Kurokawa
Division of Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.

In order to clarify the role of oxidative stress in carcinogenesis by potassium bromate (KBrO3), 8-hydroxydeoxyguanosine (8-OH-dG) levels and cumulating replicating fractions (CRFs) were measured in the kidneys and livers of F344 rats receiving gavage doses of 100, 200 or 400 mg/kg. We used female rats in this study to allow the potential of KBrO3 for inducing alpha 2u-globulin accumulation--known to result in sustained cell proliferation and eventual promoting activity in males--to be ignored. Additional female rats were given 0.05% N-ethyl-N-hydroxyethylnitrosamine (EHEN) orally for the first 2 weeks as an initiator with subsequent administration of KBrO3 at a dose of 500 p.p.m. in the drinking water for 30 weeks. 8-OH-dG levels in the kidneys were significantly elevated with doses of 200 and 400 mg/kg, and this correlated with increases of the CRFs of proximal tubules. In the livers, however, no significant changes were found. In the promotion bioassay, the mean numbers of atypical tubules, atypical hyperplasias and renal cell tumors per rat in animals treated with KBrO3 after EHEN initiation were significantly higher than those in animals receiving distilled water after EHEN initiation. In contrast, there were no significant differences between groups in terms of liver tumors. The overall data suggest that oxidative stress generated by KBrO3 exposure might be associated with induction of cell proliferation and associated promoting activity.

UI MeSH Term Description Entries
D007680 Kidney Neoplasms Tumors or cancers of the KIDNEY. Cancer of Kidney,Kidney Cancer,Renal Cancer,Cancer of the Kidney,Neoplasms, Kidney,Renal Neoplasms,Cancer, Kidney,Cancer, Renal,Cancers, Kidney,Cancers, Renal,Kidney Cancers,Kidney Neoplasm,Neoplasm, Kidney,Neoplasm, Renal,Neoplasms, Renal,Renal Cancers,Renal Neoplasm
D007684 Kidney Tubules Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER. Kidney Tubule,Tubule, Kidney,Tubules, Kidney
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008114 Liver Neoplasms, Experimental Experimentally induced tumors of the LIVER. Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D001959 Bromates Negative ions or salts derived from bromic acid, HBrO3. Bromate
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D003849 Deoxyguanosine A nucleoside consisting of the base guanine and the sugar deoxyribose.
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005260 Female Females

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