ABSTRACT
By means of the formation of SeîN, the ABT-Se and NDI-Se were developed to detect and visualize endogenous hypobromous acid (HOBr) in live cells. Specifically, the upregulation of HOBr was monitored by NDI-Se during the administration of an immunotherapeutic agent.
Subject(s)
Antineoplastic Agents/pharmacology , Bromates/chemistry , Cysteine/pharmacology , Fluorescent Dyes/chemistry , Immunotherapy , Uterine Cervical Neoplasms/drug therapy , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Bromates/administration & dosage , Cell Proliferation/drug effects , Cysteine/administration & dosage , Cysteine/chemistry , Female , Fluorescent Dyes/administration & dosage , Fluorescent Dyes/chemical synthesis , HeLa Cells , Humans , Injections, Intraperitoneal , Mice , Molecular Structure , Nitrogen/administration & dosage , Nitrogen/chemistry , Optical Imaging , Selenium/administration & dosage , Selenium/chemistry , Uterine Cervical Neoplasms/pathologyABSTRACT
In regulatory genetic toxicology, it is an axiom that there is no threshold for genotoxicity of chemicals, such that genotoxic chemicals may impose carcinogenic risk on humans even at very low doses. This paradigm is counterintuitive, however, because humans possess a number of self-defense mechanisms that may suppress the genotoxicity at these low doses and therefore manifest a practical threshold. DNA polymerase zeta (Pol ζ) is a specialized Pol that plays an important role in DNA synthesis across DNA damage, thereby modulating cell survival and genotoxicity. In this study, we compared the sensitivity of three types of human cells: D2781N, L2618M, and their wild-type (WT) cells, to the low dose effects of genotoxicity of the oxidizing agents, potassium bromate (KBrO3) and sodium dichromate (Na2Cr2O7). D2781N cells express a variant form of Pol ζ, whose activity is weaker than that of the WT enzyme. L2618M cells express another variant form of Pol ζ, whose fidelity of DNA replication is lower than that of the WT enzyme. D2781N exhibited the highest sensitivity for TK gene mutation and micronucleus (MN) formation and displayed the lowest practical threshold for MN induction by KBrO3. In contrast, L2618M exhibited the lowest practical threshold for sister-chromatid exchange (SCE) induction by both chemicals. These results suggest that Pol ζ mutations have significant impacts on practical thresholds of genotoxicity; the factors affecting the practical threshold can differ depending on the endpoint of genotoxicity. Roles of the variant forms of Pol ζ in genotoxicity by the oxidizing agents are discussed.
Subject(s)
Mutagenicity Tests/methods , Mutagens/toxicity , Mutation , 8-Hydroxy-2'-Deoxyguanosine , Bromates/administration & dosage , Bromates/toxicity , Cell Line , Chromates/administration & dosage , Chromates/toxicity , DNA Damage/genetics , DNA-Directed DNA Polymerase/genetics , Deoxyguanosine/analogs & derivatives , Dose-Response Relationship, Drug , Humans , Micronucleus Tests , Sister Chromatid Exchange/drug effects , Thymidine Kinase/geneticsABSTRACT
BACKGROUND: Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. The present study reports the side effects of KBrO3 administration on the brain functions and behaviour of albino mice. METHODS: Animals were divided into three groups: control, low dose KBrO3 (100 mg/kg/day) and high dose KBrO3 (200 mg/kg/day) groups. RESULTS: Administration of KBrO3 led to a significant change in the body weight in the animals of the high dose group in the first, second and the last weeks while water consumption was not significantly changed. Neurobehavioral changes and a reduced Neurotransmitters levels were observed in both KBrO3 groups of mice. Also, the brain level of reduced glutathione (GSH) in KBrO3 receiving animals was decreased. Histological studies favoured these biochemical results showing extensive damage in the histological sections of brain of KBrO3-treated animals. CONCLUSIONS: These results show that KBrO3 has serious damaging effects on the central nervous system and therefore, its use should be avoided.
Subject(s)
Bromates/administration & dosage , Administration, Oral , Animals , Body Weight/drug effects , Brain/drug effects , Brain/metabolism , Bromates/toxicity , Dose-Response Relationship, Drug , Food Additives/administration & dosage , Food Additives/toxicity , Glutathione/metabolism , Male , Mice , Neurotransmitter Agents/administration & dosage , Neurotransmitter Agents/toxicity , Oxidative Stress/drug effectsABSTRACT
Bromate is a byproduct of water disinfection that is produced when waters contain bromide treated with ozone. To investigate the level of the toxicity of bromate and find the most sensitive indicators in a short time, a series of toxicological assessments were conducted including the acute toxicity, cumulative toxicity, genetic toxicity and subacute toxicity of bromate (using Potassium Bromate to represent bromate). The LD50 of orally administered Potassium Bromate was 215 mg/kg in Wistar rats and 464 mg/kg in ICR mice. The cumulative toxicity of Potassium Bromate was not obvious. The Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test did not indicate mutagenicity. The results of the subacute study did not exhibit significant differences in most of the parameters, except the white blood cell count, which was significantly decreased in male rats. In addition, Potassium Bromate influenced the albumin, creatinine, total cholesterol, triglycerides and glucose levels in male rats to various extents. A thorough analysis of the above tests clearly demonstrates that bromate has toxicity, not obvious cumulative toxicity and the white blood cell count can be used as an indicator to reflect the toxicity of bromate and investigate bromate's toxic mechanism.
Subject(s)
Bromates/toxicity , Water Pollutants, Chemical/toxicity , Water Purification , Administration, Oral , Animals , Biomarkers/blood , Body Weight/drug effects , Bromates/administration & dosage , Dose-Response Relationship, Drug , Drinking , Eating/drug effects , Female , Lethal Dose 50 , Leukocytes/drug effects , Male , Mice, Inbred ICR , Micronucleus Tests , Rats, Wistar , Risk Assessment , Spermatozoa/drug effects , Spermatozoa/pathology , Time Factors , Toxicity Tests, Acute/methods , Water Pollutants, Chemical/administration & dosageABSTRACT
Non-O157 Shiga toxin-producing Escherichia coli (STEC) is an emerging risk for food safety. Although numerous postharvest antimicrobial interventions have been effectively used to control E. coli O157:H7 during beef harvesting, research regarding their effectiveness against non-O157 STEC is scarce. The objectives of this study were (i) to evaluate effects of the spray treatments-ambient water, 5% lactic acid (LA), 200 ppm of hypobromous acid (HA), and 200 ppm of peroxyacetic acid (PA)-on the reduction of O157:H7 or non-O157 STEC (O26, O103, O111, and O145) with high (10(6) log CFU/50 cm(2)) or low (10(2) log CFU/50 cm(2)) levels on beef subprimals after vacuum storage for 14 days and (ii) to evaluate the association of the antimicrobial treatments and cooking (50 or 70°C) on the reduction of the pathogens in blade-tenderized steaks. The treatment effects were only observed (P = 0.012) on samples taken immediately after spray intervention treatment following inoculation with a high level of O157:H7. The LA and PA treatments significantly reduced low-inoculated non-O157 STEC after spray intervention; further, the LA and HA treatments resulted in significant reductions of non-O157 STEC on the low-inoculated samples after storage. Although cooking effectively reduced the detection of pathogens in internal steak samples, internalized E. coli O157:H7 and non-O157 STEC were able to survive in steaks cooked to a medium degree of doneness (70°C). This study indicated that the reduction on surface populations was not sufficient enough to eliminate the pathogen's detection following vacuum storage, mechanical tenderization, and cooking. Nevertheless, the findings of this study emphasize the necessity for a multihurdle approach and further investigations of factors that may influence thermal tolerance of internalized pathogenic STEC.
Subject(s)
Anti-Infective Agents/pharmacology , Escherichia coli O157/drug effects , Escherichia coli/drug effects , Meat/microbiology , Shiga-Toxigenic Escherichia coli/drug effects , Animals , Bromates/administration & dosage , Cattle , Colony Count, Microbial , Cooking , Escherichia coli/isolation & purification , Escherichia coli O157/isolation & purification , Food Handling/instrumentation , Food Handling/methods , Food Microbiology , Food Safety , Food Storage/methods , Hot Temperature , Lactic Acid/administration & dosage , Peracetic Acid/administration & dosage , Shiga-Toxigenic Escherichia coli/isolation & purification , VacuumABSTRACT
The time dependent effect of orally administered KBrO(3) on redox status and enzymes of brush border membrane (BBM) and carbohydrate metabolism has been studied in rat kidney. Animals were given a single oral dose of KBrO(3) (100mg/kg body weight) and sacrificed at different times after this treatment; control animals were not given KBrO(3). The administration of KBrO(3) resulted in nephrotoxicity, a decline in the specific activities of several BBM marker enzymes and also induced oxidative stress in kidney. The specific activities of enzymes of carbohydrate metabolism were also altered and suggest a shift in energy metabolism from the aerobic to anaerobic mode. The renal effects of single oral dose of KBrO(3) appeared to be reversible; maximum changes in all the parameters were 48 h after administration of KBrO(3) after which recovery took place, in many cases almost to control values, after 168 h. These results suggest that the administration of a single nephrotoxic dose of KBrO(3) inhibits brush border membrane enzymes, induces oxidative stress and alters energy metabolism of the renal system in a reversible manner.
Subject(s)
Bromates/administration & dosage , Cell Membrane/enzymology , Food Additives/administration & dosage , Kidney/drug effects , Kidney/metabolism , Administration, Oral , Animals , Bromates/toxicity , Carbohydrate Metabolism/drug effects , Cell Membrane/drug effects , Cell Membrane/metabolism , Down-Regulation/drug effects , Food Additives/toxicity , Kidney/enzymology , Male , Malondialdehyde/metabolism , Microvilli/drug effects , Microvilli/enzymology , Microvilli/metabolism , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Rats , Rats, WistarABSTRACT
The acute toxicity of potassium bromate (KBrO(3)) on rat small intestine was studied in this work. Animals were given a single oral dose of KBrO(3) (100 mg/kg body weight) and sacrificed 12, 24, 48, 96 and 168 h after the treatment; control animals were not given KBrO(3). The administration of KBrO(3) resulted in a reversible decline in the specific activities of several BBM enzymes. Lipid peroxidation, protein oxidation and hydrogen peroxide levels increased while total sulfhydryl groups and reduced glutathione decreased in KBrO(3)-treated rats indicating induction of oxidative stress in the intestinal mucosa. The activities of anti-oxidant and carbohydrate metabolic enzymes were also altered upon KBrO(3) treatment. The maximum changes in all the parameters were 48 h after administration of KBrO(3) after which recovery took place, in many cases almost to control values after 168 h. Histopathological studies supported the biochemical findings showing extensive damage to the intestine at 48 h and recovery at 168 h. These results show that a single oral dose of KBrO(3) causes reversible oxidative damage to the intestine.
Subject(s)
Bromates/toxicity , Carbohydrate Metabolism/drug effects , Intestine, Small/drug effects , Oxidative Stress/drug effects , Administration, Oral , Alkaline Phosphatase/metabolism , Animals , Bromates/administration & dosage , Carcinogens/administration & dosage , Carcinogens/toxicity , Catalase/metabolism , Glutathione/metabolism , Glutathione Transferase/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/enzymology , Intestinal Mucosa/metabolism , Intestine, Small/enzymology , Intestine, Small/metabolism , Lipid Peroxidation/drug effects , Male , Malondialdehyde/metabolism , Microvilli/drug effects , Microvilli/enzymology , Microvilli/metabolism , Oxidation-Reduction/drug effects , Rats , Rats, Wistar , Sucrase/metabolism , Superoxide Dismutase/metabolism , Time FactorsABSTRACT
UNLABELLED: Bromate is a drinking water disinfection by-product formed during the ozonation of source water containing bromide. Sodium bromate is also used as an analytical reagent, in the oxidation of sulfur and vat dyes, and for cleaning boilers. As a mixture with sodium bromide, it is used for dissolving gold from its ores. The cosmetic industry uses sodium bromate and potassium bromate as neutralizers or oxidizers in hair wave preparations. Sodium bromate was nominated for toxicity and carcinogenicity studies in transgenic mouse models by the United States Environmental Protection Agency and the National Institute of Environmental Health Sciences. Male and female Tg.AC hemizygous mice received sodium bromate by dermal application for 26 or 39 weeks and by exposure in drinking water for 27 or 43 weeks. Male and female p53 haploinsufficient mice were exposed to sodium bromate (at least 99% pure) in drinking water for 27 or 43 weeks. Genetic toxicology studies were conducted in mouse peripheral blood erythrocytes. 26- and 39-WEEK DERMAL STUDIES IN Tg.AC HEMIZYGOUS MICE: Groups of 15 male and 15 female Tg.AC hemizygous mice received dermal applications of 0, 64, 128, or 256 mg sodium bromate/kg body weight in ethanol/water, 5 days per week for 26 weeks. Additional groups of 10 male and 10 female Tg.AC hemizygous mice were dermally administered the same doses for 39 weeks. Survival of dosed groups was similar to that of vehicle control groups at 26 and 39 weeks. Mean body weights of 256 mg/kg males were less than those of the vehicle control group in both studies. Mean body weights of all dosed groups of females were less than those of the vehicle controls at 39 weeks. Minimal decreases in hematocrit and hemoglobin concentration values occurred in 128 mg/kg females and 256 mg/kg males and females at 26 weeks. A minimal decrease in erythrocyte count also occurred in 256 mg/kg males. These decreases in erythron were accompanied by a minimal decrease in mean cell hemoglobin and mean cell hemoglobin concentration values, primarily in the females. Reticulocyte counts were significantly increased in 128 mg/kg females and 256 mg/kg males and females. There were no increased incidences of neoplasms in male or female Tg.AC hemizygous mice exposed to sodium bromate dermally. Relative kidney weights were significantly increased in 256 mg/kg males at 26 weeks and in all dosed groups of males at 39 weeks. Absolute testis weights in 256 mg/kg males and absolute kidney weights in 256 mg/kg females were decreased at 39 weeks. Nephropathy occurred in 14 of 15 males receiving 128 and 256 mg/kg at 26 weeks and in all 256 mg/kg females in both studies. In the thyroid gland, the incidences of follicular cell hypertrophy in all dosed groups of males and females, follicular secretory depletion in 128 and 256 mg/kg females, and lymphocytic cellular infiltrate in 256 mg/kg females were significantly increased in both studies. Splenic hematopoietic cell proliferation occurred with a significantly increased incidence in 128 and 256 mg/kg females at 26 weeks. The incidence of germinal epithelium degeneration in the testis was significantly increased in 256 mg/kg males at 39 weeks. 27- AND 43-WEEK DRINKING WATER STUDIES IN Tg.AC HEMIZYGOUS MICE: Groups of 15 male and 15 female Tg.AC hemizygous mice were exposed to drinking water containing 0, 80, 400, or 800 mg/L sodium bromate for 27 weeks (equivalent to average daily doses of approximately 13, 63, and 129 mg/kg to male mice and 15, 72, and 148 mg/kg to female mice). Additional groups of 10 male and 10 female Tg.AC hemizygous mice were exposed to drinking water containing 0, 80, 400, or 800 mg/L sodium bromate for 43 weeks (equivalent to average daily doses of approximately 11, 52, and 131 mg/kg to male mice and 15, 65, and 152 mg/kg to female mice). Survival of exposed groups was similar to that of control groups at 27 weeks. Survival was decreased in 400 mg/L females and 800 mg/L males and females at 43 weeks. Mean body weights of 400 mg/L males and 800 mg/L males and females were less than those of the control groups in both studies. Water consumption by exposed mice was generally similar to that by control groups throughout both studies. Minimal decreases in hematocrit, hemoglobin concentration, and erythrocyte count values occurred primarily in 400 and 800 mg/kg females at 27 weeks. There were also decreases in mean cell hemoglobin and mean cell hemoglobin concentration values, but these occurred primarily in treated males. Reticulocyte counts were increased in 400 mg/kg males and 800 mg/kg males and females. There were no increased incidences of neoplasms in male or female Tg.AC hemizygous mice exposed to sodium bromate in the drinking water. Absolute kidney weights were significantly decreased in 800 mg/L females and relative kidney weights were increased in 400 and 800 mg/L males at 27 weeks. Absolute testis weights were significantly decreased in 800 mg/L males at 43 weeks. Thyroid gland follicular cell hypertrophy and follicular secretory depletion occurred in most 400 and 800 mg/L males and females at 27 weeks and in most exposed females at 43 weeks, and the incidences of thyroid gland follicular cell hypertrophy were significantly increased in all exposed groups of males at 43 weeks. The incidences of thyroid gland lymphocytic cellular infiltrates were significantly increased in 400 and 800 mg/L females in both studies and in 800 mg/L males at 43 weeks. The incidences of nephropathy were significantly increased in all exposed groups of males and in 400 and 800 mg/L females at 27 weeks. Renal tubule degeneration occurred with significantly increased incidences in 800 mg/L males and females in both studies. The incidences of renal tubule hypertrophy were significantly increased in 400 and 800 mg/L females at 27 weeks and in 800 mg/L males and females at 43 weeks. Pituitary gland pars distalis hypertrophy occurred with a significantly increased incidence in 800 mg/L females in both studies. The incidence of hyperkeratosis of the forestomach epithelium was significantly increased in 800 mg/L females at 43 weeks. The incidences of tubular degeneration of the epididymis and germinal epithelium degeneration of the testis were significantly increased in 800 mg/L males at 43 weeks. 27- AND 43-WEEK DRINKING WATER STUDIES IN p53 HAPLOINSURFFICIENT MICE: Groups of 15 male and 15 female p53 haploinsufficient mice were exposed to drinking water containing 0, 80, 400, or 800 mg/L sodium bromate for 27 weeks (equivalent to average daily doses of approximately 8, 39, and 74 mg/kg to males and 13, 72, and 136 mg/kg to females). Additional groups of 10 male and 10 female p53 haploinsufficient mice were exposed to drinking water containing 0, 80, 400, or 800 mg/L sodium bromate for 43 weeks (equivalent to average daily doses of approximately 7, 37, and 65 mg/kg to males and 11, 58, and 107 mg/kg to females). In both studies, survival of exposed groups was similar to that of control groups. Mean body weights of 400 and 800 mg/L females were less than those of the control groups during most of the studies. Water consumption by exposed mice was generally similar to that by control groups in both studies. No neoplasms or nonneoplastic lesions in male or female p53 haploinsufficient mice were attributed to exposure to sodium bromate in either study. GENETIC TOXICOLOGY: Sodium bromate exposure resulted in significantly increased frequencies of micronucleated erythrocytes in male and female Tg.AC hemizygous and p53 haploinsufficient mice administered the chemical in drinking water for 27 weeks or by dermal application for 26 weeks. Tg.AC hemizygous mice were treated by both routes; p53 haploinsufficient mice were exposed only through drinking water. In all three micronucleus tests, a clear dose response was observed in male and female mice. Significant increases in the percentage of polychromatic erythrocytes among total erythrocytes were observed in male and female Tg.AC hemizygous mice exposed via drinking water and in male Tg.AC hemizygous mice dosed dermally with sodium bromate. The percentage of polychromatic erythrocytes was not significantly altered in male or female p53 mice. CONCLUSIONS: Under the conditions of these drinking water studies, there was no evidence of carcinogenic activity of sodium bromate in male or female p53 haploinsufficient mice exposed to 80, 400, or 800 mg/L for 27 or 43 weeks. No treatment-related neoplasms were seen in male or female Tg.AC hemizygous mice exposed dermally to 64, 128, or 256 mg sodium bromate/kg body weight for 26 or 39 weeks. No treatment-related neoplasms were seen in male or female Tg.AC hemizygous mice exposed by drinking water to 80, 400, or 800 mg sodium bromate/L for 27 or 43 weeks. In drinking water and dermal studies in Tg.AC hemizygous mice there were increased incidences of nonneoplastic lesions in the thyroid gland and kidney.
Subject(s)
Bromates/toxicity , Sodium Compounds/toxicity , Water Pollutants, Chemical/toxicity , Administration, Cutaneous , Animals , Body Weight/drug effects , Bromates/administration & dosage , Carcinogenicity Tests , Female , Genes, ras/genetics , Kidney/drug effects , Kidney/pathology , Male , Mice , Mice, Transgenic , Sodium Compounds/administration & dosage , Thyroid Gland/drug effects , Thyroid Gland/pathology , Tumor Suppressor Protein p53/genetics , Water SupplyABSTRACT
Potassium bromate (KBrO(3)) is classified as a carcinogenic agent. KBrO(3) induces tumors and pro-oxidative effects in kidneys. Melatonin is a well known antioxidant and free radical scavenger. Indole-3-propionic acid (IPA), an indole substance, also reveals antioxidative properties. Recently, some antioxidative effects of propylthiouracil (PTU)-an antithyroid drug-have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the kidneys and blood serum and, additionally, in the livers and the lungs, collected from rats, pretreated with KBrO(3). Male Wistar rats were administered KBrO(3) (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). The level of lipid peroxidation products-malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA)-was measured spectrophotometrically in thyroid homogenates. KBrO(3), when injected to rats, significantly increased lipid peroxidation in the kidney homogenates and blood serum, but not in the liver and the lung homogenates. Co-treatment with either melatonin or with IPA, but not with PTU, decreased KBrO(3)-induced oxidative damage to lipids in the rat kidneys and serum. In conclusion, melatonin and IPA, which prevent KBrO(3)-induced lipid peroxidation in rat kidneys, may be of great value as protective agents under conditions of exposure to KBrO(3).
Subject(s)
Bromates/administration & dosage , Indoles/pharmacology , Kidney/metabolism , Lipid Peroxidation/drug effects , Melatonin/pharmacology , Administration, Oral , Animals , Kidney/drug effects , Male , Propylthiouracil/pharmacology , Rats , Rats, WistarABSTRACT
It is still of importance to investigate renal carcinogenesis by potassium bromate (KBrO3), a by-product of water disinfection by ozonation, for assessment of the risk to man. Five female F344 rats in each group were given KBrO3 at a dose of 300 mg/kg by single i.g. intubation or at a dose of 80 mg/kg by single i.p. injection, and were killed 48 h after the administration for measurements of thiobarbituric acid-reactive substances (TBARS) and 8-oxodeoxyguanosine (8-oxodG) levels in the kidney. Both levels in the treated animals were significantly elevated as compared with the control values. In a second experiment, 5 male and female F344 rats in each group were administered KBrO3 at concentrations of 0, 15, 30, 60, 125, 250 and 500 ppm in the drinking water for 4 weeks. KBrO3 in the drinking water did not elevate TBARS in either sex at any of the doses examined, but 8-oxodG formation in both sexes at 250 ppm and above was significantly higher than in the controls. Additionally, the bromodeoxyuridine-labeling index for proximal convoluted tubules was significantly increased at 30 ppm and above in the males, and at 250 ppm and above in the females. Alpha2u-globulin accumulation in the kidneys of male rats was increased with statistical significance at 125 ppm and above. These findings suggest that DNA oxidation induced by KBrO3 may occur independently of lipid peroxidation and more than 250 ppm KBrO3 in the drinking water can exert a carcinogenic effect by way of oxidative stress.
Subject(s)
Bromates/toxicity , Carcinogens/toxicity , Cell Division/drug effects , Kidney Neoplasms/chemically induced , Kidney/cytology , Kidney/pathology , Oxidative Stress , Administration, Oral , Animals , Bromates/administration & dosage , Carcinogens/administration & dosage , DNA Damage , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Humans , Lipid Peroxidation , Male , Rats , Rats, Inbred F344 , Water PurificationABSTRACT
Iodine could be added to the diet of human population in the form of iodide or iodate but iodate had not been adequately tested for genotoxicity and carcinogenicity. In the present study, genotoxic effects of potassium iodate were evaluated in vitro using the alkaline comet assay and the cytokinesis-block micronucleus assay on CHO cells and compared to halogenate salt analogues potassium bromate and chlorate and also to their respective reduced forms (potassium iodide, bromide and chloride). The results showed that the comet assay failed to detect the presence of DNA damage after a treatment of cells by potassium iodate for concentrations up to 10 mM. This absence of primary DNA damage was confirmed in the cytokinesis-block micronucleus assay. In the same way, results showed that potassium chlorate as well as potassium iodide, bromide and chloride did not induced DNA damage in the alkaline comet assay for doses up to 10 mM. By contrast, potassium bromate exposure led to an increase in both DNA damage and frequency of micronucleated cells. The repair of bromate-induced DNA damage was incomplete 24 h after the end of treatment. These results seem to indicate that potassium bromate would induce DNA damage by several mechanisms besides oxidative stress.
Subject(s)
Bromates/toxicity , Iodates/toxicity , Potassium Compounds/toxicity , Animals , Bromates/administration & dosage , CHO Cells/drug effects , Comet Assay , Cricetinae , Cricetulus , Female , Iodates/administration & dosage , Micronucleus Tests , Potassium Compounds/administration & dosageABSTRACT
Plant-derived polyphenolics and other chemicals with antioxidant properties have been reported to inhibit the expression of genotoxic activity by pro-oxidant chemicals (Sai et al., 1992, 1994; Teel and Castonguay, 1992). In vitro and in vivo studies with ionizing radiation suggest that hydroquinone (HQ) may have similar protective effects (Babaev et al., 1994). The present study was conducted to determine whether HQ is capable of inhibiting the induction of micronuclei in the bone marrow of mice following exposure to an oxidant, potassium bromate or KBrO3 (Nakajima et al., 1989; Sai et al., 1992, 1994). To be able to interpret the results of this work, it was also necessary to determine whether HQ is itself genotoxic when fed in the diet. HQ diets (0.8%) fed to mice for 6 days reduced the background incidence of micronuclei compared with the basal diet. KBrO3 dosed ip (12.5-100 mg/kg) produced a dose-dependent increase in micronuclei as reported by others. Mice fed 0.8% HQ diets 6 days, and then dosed intraperitoneally with KBrO3, showed a 36% reduction in micronuclei across the range of KBrO3 dose levels. This effect was associated with a reduction in the background micronucleus response as well as a reduction in response to KBrO3. Statistical significance (P < or = 0.05), observed at a dose of 25 mg/kg KBrO3 in the mice fed the control diet, was abolished in the group fed 0.8% HQ. When mice were given 50 mg HQ/kg by oral gavage and then given 50 mg KBrO3/kg ip 20 min later, the micronucleus response induced by KBrO3, was lower in animals given HQ. The results of this study demonstrate that large doses of HQ may be given orally without induction of micronuclei or bone marrow depression, that HQ reduces the background micronucleus response in animals fed a basal diet, and that the HQ reduces the micronucleus response to KBrO3 as well as background incidence of micronuclei in KBrO3-dosed animals. The protective effect of HQ may be due to enzyme induction or a direct antioxidant effect of HQ against oxidants commonly present in the diet.
Subject(s)
Antimutagenic Agents/pharmacology , Bromates/toxicity , Hydroquinones/pharmacology , Mutagens/toxicity , Administration, Oral , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/ultrastructure , Bromates/administration & dosage , Diet , Drug Interactions , Female , Hydroquinones/administration & dosage , Hydroquinones/blood , Injections, Intraperitoneal , Male , Mice , Micronucleus TestsABSTRACT
Potassium bromate (KBrO3) is a rodent carcinogen and a nephro- and neurotoxicant in humans. KBrO3 is used in cosmetics and food products and is a by-product of water disinfection by ozonization. KBrO3 is carcinogenic in the rat kidney, thyroid, and mesothelium and is a renal carcinogen in the male mouse. The present study was designed to investigate the relationship of time and dose to bromate-induced tumors in male Fischer 344 (F344) rats and to provide some insight into the development of these tumors. KBrO3 was dissolved in drinking water at nominal concentrations of 0, 0.02, 0.1, 0.2, and 0.4 g/L and administered to male F344 rats as the sole water source for 12, 26, 52, 78, or 100 wk. Renal cell tumors were present after 52 wk of treatment only in the high-dose group. Mesotheliomas developed after 52 wk of treatment on the tunica vaginalis. Mesotheliomas were present at sites other than the testicle after 78 wk of treatment, indicating that their origin was the testicular tunic. Thyroid follicular tumors were present as early as 26 wk in 1 rat each from the 0.1- and 0.2-g/L groups. The present study can be used as a basis for the determination of dose-time relationships of tumor development for a better understanding of KBrO3-induced cancer.
Subject(s)
Bromates/toxicity , Carcinogens/toxicity , Neoplasms/chemically induced , Adenoma/blood , Adenoma/chemically induced , Adenoma/pathology , Animals , Bromates/administration & dosage , Carcinogens/administration & dosage , Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/chemically induced , Carcinoma, Renal Cell/pathology , Dose-Response Relationship, Drug , Kidney Neoplasms/blood , Kidney Neoplasms/chemically induced , Kidney Neoplasms/pathology , Male , Mesothelioma/blood , Mesothelioma/chemically induced , Mesothelioma/pathology , Neoplasms/blood , Neoplasms/pathology , Rats , Rats, Inbred F344 , Testicular Neoplasms/blood , Testicular Neoplasms/chemically induced , Testicular Neoplasms/pathology , Thyroid Neoplasms/blood , Thyroid Neoplasms/chemically induced , Thyroid Neoplasms/pathology , Thyroxine/blood , Time Factors , Triiodothyronine/bloodABSTRACT
Ozone has been proposed for water disinfection because it is more efficient than chlorine for killing microbes and results in much lower levels of carcinogenic trihalomethanes than does chlorination. Ozone leads to formation of hypobromous acid in surface waters with high bromine content and forms brominated organic by-products and bromate. The carcinogenicity and chronic toxicity of potassium bromate (KBrO3) was studied in male B6C3F1 mice and F344/N rats to confirm and extend the results of previous work. Mice were treated with 0, 0.08, 0.4, or 0.8 g/L KBrO3 in the drinking water for up to 100 wk, and rats were provided with 0, 0.02, 0.1, 0.2, or 0.4 g/L KBrO3. Animals were euthanatized, necropsied, and subjected to a complete macroscopic examination. Selected tissues and gross lesions were processed by routine methods for light microscopic examination. The present study showed that KBrO3 is carcinogenic in the rat kidney, thyroid, and mesothelium and is a renal carcinogen in the male mouse, KBrO3 was carcinogenic in rodents at water concentrations as low as 0.02 g/L (20 ppm; 1.5 mg/kg/day). These data can be used to estimate the human health risk that would be associated with changing from chlorination to ozonation for disinfection of drinking water.
Subject(s)
Bromates/toxicity , Carcinogens/toxicity , Animals , Body Weight/drug effects , Bromates/administration & dosage , Dose-Response Relationship, Drug , Drinking , Eating/drug effects , Male , Mice , Mice, Inbred Strains , Neoplasms, Experimental/blood , Neoplasms, Experimental/chemically induced , Neoplasms, Experimental/pathology , Organ Size/drug effects , Rats , Rats, Inbred F344 , WaterABSTRACT
Realizaram-se análises estatísticas de dados referentes à composiçäo bromatológica e ao coeficiente de digestibilidade (CD) de 29 diferentes tipos de dietas utilizadas em 383 ensaios de digestibilidade, recolhidos de 91 trabalhos científicos realizados com equinos, para encontrar correlaçöes entre a fraçäo fibrosa dos alimentos e sua energia digestível (ED, Mcal/kg MS), que permitissem a obtençäo de equaçöes de prediçäo da ED, do CD da energia (CDE) e do CD da matéria orgânica (CDMO) em funçäo do teor de fibra bruta (FB), fibra em detergente neutro (FDN), fibra em detergente ácido (FDA), hemicelulose (HCEL), celulose (CEL) e lignina (LIG) dos alimentos. A análise de regressäo linear simples para todos os tipos de dietas forneceu as seguintes equaçöes: ED = -0,1040 + 0,0416 CDMO (R ao quadrado = 85 por cento); ED = 3,7868-0,0440 FDA (R ao quadrado = 87 por cento); CDE = 86,0261-0,9495 FDA (R ao quadrado = 75 por cento); CDMO = 89,9290-0,9098 FDA (R ao quadrado = 83 por cento); CDMO = 89,0107-1,0916 CEL (R ao quadrado = 89 por cento). A análise de regressäo linear múltipla forneceu apenas uma equaçäo ED = 5,0285-0,0424 FDA-0,0144 MO (R ao quadrado = 89 por cento), para dietas completas. Quando se dividiu as dietas em duas classes, de volumosos e de volumosos mais concentrados, foram obtidas as seguintes equaçöes de regressäo linear simples, que podem ser aplicadas às dietas compostas por volumosos mais concentrados: CDE = 90,3526-1,1551 FDA (R ao quadrado = 79 por cento); CDMO = 90,8290-0,9379 FDA (R ao quadrado = 92 por cento); CDMO = 88,9743-0,9561 CEL (R ao quadrado = 96 por cento); CDMO = 84,8783-4,5545 LIG (R ao quadrado = 90 por cento)
Subject(s)
Animals , Animal Nutritional Physiological Phenomena , Bromates/administration & dosage , Dietary Fiber/administration & dosage , Digestion , Electric Power Supplies , HorsesABSTRACT
The effect of intraperitoneal injection (i.p.) versus oral gavage administration (p.o.) of potassium bromate was examined using the micronucleus test in 2 strains of male mice (MS/Ae and CD-1). First, a small acute toxicity test and a pilot micronucleus experiment were performed to determine the appropriate dose range and sampling time for the full-scale micronucleus test. The full-scale test was carried out using doses of 18.8, 37.5, 75, and 150 mg/kg in the i.p. test and of 37.5, 75, 150, and 300 mg/kg in the p.o. test. The sampling time was 24 h for both mouse strains. Potassium bromate induced micronucleated polychromatic erythrocytes (MNPCEs) dose-dependently by both routes of administration in both mouse strains. No distinct difference in route of administration was observed in the test with MS/Ae mice. In CD-1 mice more MNPCEs were induced by the i.p. route than by the p.o. route.
Subject(s)
Bromates/administration & dosage , Bromine/administration & dosage , Micronucleus Tests , Mutagens/administration & dosage , Administration, Oral , Animals , Bromates/toxicity , Injections, Intraperitoneal , Lethal Dose 50 , Male , Mice , Pilot ProjectsABSTRACT
The acute cytogenetic effects of potassium bromate (KBrO3) on rat bone marrow cells in vivo were studied. The incidence of chromosome aberrations in bone marrow cells increased rapidly, reaching a maximum level 12 h after intraperitoneal injection and decreased within 24 h. Dose-response relationships were obtained for both intraperitoneal and oral administrations.
Subject(s)
Bone Marrow/drug effects , Bromates/pharmacology , Bromine/pharmacology , Chromosome Aberrations , Administration, Oral , Animals , Bromates/administration & dosage , Cells, Cultured , Dose-Response Relationship, Drug , Hot Temperature , Injections, Intraperitoneal , Male , RatsABSTRACT
Following oral administration of a renal carcinogen, potassium bromate (KBrO3), to the rat, a significant increase of 8-hydroxydeoxyguanosine (8-OH-dG) in kidney DNA was observed. In the liver, a non-target tissue, the increase in 8-OH-dG was not significant. The non carcinogenic oxidants, NaCIO and NaCIO2, had no effect on 8-OH-dG formation in kidney DNA. These results suggest that formation of 8-OH-dG in tissue DNA is closely related to KBrO3 carcinogenesis.