Induction of micronucleated reticulocytes by potassium bromate and potassium chromate in CD-1 male mice

Awogi, Takumi; Murata, Kei; Uejima, Motoo; Kubo, Takashi; Asanami, Shougo; Shimono, Kazuyuki; Morita, Takeshi

doi:10.1016/0165-1218(92)90231-n

Cited by 20 publications

(10 citation statements)

References 6 publications

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“…Another similar study performed by Awogi et al [1992] examined peripheral blood PCE for MN formation after in vivo exposure to KBrO 3 . CD‐1 male mice were dosed by single intraperitoneal injections administering KBrO 3 at doses ranging from 18.8 to 212 mg/kg [Awogi et al,1992]. Blood was collected 0–96 hr after injection of KBrO 3 .…”

Section: Resultsmentioning

confidence: 99%

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Dose‐response analysis of bromate‐induced DNA damage and mutagenicity is consistent with low‐dose linear, nonthreshold processes

Spassova

Miller

Eastmond

et al. 2012

Environ and Mol Mutagen

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Mutagenic agents have long been inferred to act through low-dose linear, nonthreshold processes. However, there is debate about this assumption, with various studies interpreting datasets as showing thresholds for DNA damage and mutation. We have applied rigorous statistical analyses to investigate the shape of dose-response relationships for a series of in vitro and in vivo genotoxicity studies using potassium bromate (KBrO(3) ), a water ozonation byproduct that is bioactivated to a reactive species causing oxidative damage to DNA. We analyzed studies of KBrO(3) genotoxicity where no-effect/threshold levels were reported as well as other representative datasets. In all cases, the data were consistent with low-dose linear models. In the majority of cases, the data were fit either by a linear (straight line) model or a model which was linear at low doses and showed a saturation-like downward curvature at high doses. Other datasets with apparent upward curvature were still adequately represented by models that were linear at low dose. Sensitivity analysis of datasets showing upward curvature revealed that both low-dose linear and nonlinear models provide adequate fits. Additionally, a simple biochemical model of selected key processes in bromate-induced DNA damage was developed and illustrated a situation where response for early primary events suggested an apparent threshold while downstream events were linear. Overall, the statistical analyses of DNA damage and mutations induced by KBrO(3) are consistent with a low-dose linear response and do not provide convincing evidence for the presence of a threshold.

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Section: Resultsmentioning

confidence: 99%

“…Data on peripheral blood normochromatic erythrocytes have been fitted with a Michaelis‐Menten model. B: Micronucleus test results from the peripheral blood polychromatic erythrocytes of CD‐1 male mice dosed with KBrO 3 (mg/kg) by intraperitoneal injection [Awogi et al,1992]. The blood was collected 24 hr after the KBrO 3 injection.…”

Section: Resultsmentioning

confidence: 99%

Dose‐response analysis of bromate‐induced DNA damage and mutagenicity is consistent with low‐dose linear, nonthreshold processes

Spassova

Miller

Eastmond

et al. 2012

Environ and Mol Mutagen

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“…While renal toxicity is a hallmark of KBrO 3 exposure, this compound is also found in many other organs of treated rodents including liver, thyroid and testes (Delker, et al, 2006). Bromate treatment also increases the incidence of micronuclei, a sign of DNA damage, in the blood (Awogi, et al, 1992; Hayashi, et al, 1989) and bone marrow (Hayashi, et al, 1988) of treated mice, and increases the incidence not only of kidney tumors, but peritoneal mesotheliomas and thyroid tumors in rats as well (DeAngelo, et al, 1998; Kurokawa, et al, 1986). KBrO 3 is unusual amongst oxidizing agents in that the predominant oxidized base it generates in DNA is 7,8-dihydro-8-oxo-guanine (8-oxoG) (Ballmaier and Epe, 2006; Kawanishi and Murata, 2006).…”

Section: Introductionmentioning

confidence: 99%

Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model

Entezam

Lokanga

et al. 2010

Hum. Mutat.

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Tandem repeat expansion is responsible for the Repeat Expansion Diseases, a group of human genetic disorders that includes Fragile X syndrome. FXS results from expansion of a premutation (PM) allele having 55-200 CGG•CCG-repeats in the 5' UTR of the FMR1 gene. The mechanism of expansion is unknown. We have treated FX PM mice with potassium bromate (KBrO 3 ), a potent DNA oxidizing agent. We then monitored the germline and somatic expansion frequency in the progeny of these animals. We show here that KBrO 3 increased both the level of 8-oxoG in the oocytes of treated animals and the germline expansion frequency. Our data thus suggest that oxidative damage may be a factor that could affect expansion risk in humans.

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“…Hence, the compound directly or indirectly (by its generated ROS) interfere or compromise the biological efficacy of many of the critical proteins and allied macromolecules disrupting many of the cellular functions ([ 38 ]a). All these cellular events consequently implicate the mutagenic and carcinogenic potentials of PB during its overdose or extended stay in the biological system [ 39 , 40 ]. The results also show hepatotoxicity of PB prominently by elevating oxidative stress and affecting the essential macromolecules as well as distortion of structural components of the target cells.…”

Section: Discussionmentioning

confidence: 99%

The Alleviative Effect of Vitamin B₂ on Potassium Bromate-Induced Hepatotoxicity in Male Rats

Hassan

Ebaid

Alhazza

et al. 2020

BioMed Research International

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Potassium bromate (PB) is a food enhancer, water disinfection by-product, and a proven carcinogen. It elicits toxicities in the living organism due to exposure and in a dose-dependent manner. The present study discourses the ameliorative efficacy of riboflavin (RF) in PB-administered rodents. The animals were distributed into five treatment groups: control (group I), PB alone (group II, 150 mg/kg), RF alone (group III, 2 mg/kg), PB+RF1 (group IV, 150 mg/kg+2 mg/kg), and PB+RF2 (group V, 150 mg/kg+4 mg/kg). After the round of the treatment, the animals were sacrificed to collect their blood and liver samples for the detailed analysis. Group II depicted perturbed liver functions evidenced by altered serum and toxicity markers along with the disturbed redox balance. Also, these biochemical results were found harmonious with histopathological analysis and comet assay. However, group III showed no noticeable alteration in the same parameters, whereas the combination groups (IV and V) exhibited dose-dependent amelioration in the PB-induced toxicities. Interestingly, RF favored apoptosis concomitant with suppressing the necrosis in the PB-challenged groups, as shown by the activity of caspase-3 and lactate dehydrogenase. Histopathological analysis and comet assay further consolidate these results. Hence, RF has significant alleviative property against PB-induced hepatotoxicity in vivo that can be used in the consumer items containing the toxicant.

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Induction of micronucleated reticulocytes by potassium bromate and potassium chromate in CD-1 male mice

Cited by 20 publications

References 6 publications

Dose‐response analysis of bromate‐induced DNA damage and mutagenicity is consistent with low‐dose linear, nonthreshold processes

Dose‐response analysis of bromate‐induced DNA damage and mutagenicity is consistent with low‐dose linear, nonthreshold processes

Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model

The Alleviative Effect of Vitamin B₂ on Potassium Bromate-Induced Hepatotoxicity in Male Rats

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Induction of micronucleated reticulocytes by potassium bromate and potassium chromate in CD-1 male mice

Cited by 20 publications

References 6 publications

Dose‐response analysis of bromate‐induced DNA damage and mutagenicity is consistent with low‐dose linear, nonthreshold processes

Dose‐response analysis of bromate‐induced DNA damage and mutagenicity is consistent with low‐dose linear, nonthreshold processes

Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model

The Alleviative Effect of Vitamin B2 on Potassium Bromate-Induced Hepatotoxicity in Male Rats

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The Alleviative Effect of Vitamin B₂ on Potassium Bromate-Induced Hepatotoxicity in Male Rats