Time- and Dose-Dependent Development of Potassium Bromate-Induced Tumors in Male Fischer 344 Rats

Wolf, Douglas C.; Crosby, Lynn M.; George, Michael H.; Kilburn, Steve R.; Moore, T.; Miller, Richard T.; DeAngelo, Anthony B.

doi:10.1177/019262339802600602

Cited by 60 publications

(43 citation statements)

References 20 publications

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“…34,35 In the renal carcinogenesis model, an iron-catalyzed Fenton reaction is repeatedly induced in the target renal proximal tubular cells early in carcinogenesis [36][37][38] These data strongly suggest that ironmediated oxidative DNA damage is a major cause of the homozygous deletion of CDKN2A/2B. Interestingly, potassium bromate shares with iron compounds the ability to cause not only mesothlioma 28 but also renal cell carcinoma 39 presumably by oxidative stress. 40 For the homozygous deletion to occur, DNA doublestrand breaks (DSBs) should be present, either as DNA damage or endogenous mechanisms.…”

Section: Discussionmentioning

confidence: 95%

“…Fischer-344 strain rats are known to generate testicular mesothelioma albeit at a low incidence (0-1.3%). 27,28 To control this situation, we have used F1 hybrid rats crossed between Fischer-344 and BrownNorway strains, and the hybrid animals in these experiments presented no mesothelioma in the untreated control group. Therefore, we believe that our data was not affected significantly by the background of genetic susceptibility to mesothelioma.…”

Section: Discussionmentioning

confidence: 99%

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Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Akatsuka

Yamashita

et al. 2010

Laboratory Investigation

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In humans, mesothelioma has been linked to asbestos exposure, especially crocidolite and amosite asbestos, which contain high amounts of iron. Previously, we established a rat model of iron-induced peritoneal mesothelioma with repeated intraperitoneal injections of iron saccharate and an iron chelator, nitrilotriacetate. Here, we analyze these mesotheliomas using array-based comparative genomic hybridization (aCGH) and gene expression profiling by microarray. Mesotheliomas were classified into two distinct types after pathologic evaluation by immunohistochemistry. The major type, epithelioid mesothelioma (EM), originated in the vicinity of tunica vaginalis testis, expanded into the upper peritoneal cavity and exhibited papillary growth and intense podoplanin immunopositivity. The minor type, sarcomatoid mesothelioma (SM), originated from intraperitoneal organs and exhibited prominent invasiveness and lethality. Both mesothelioma types showed male preponderance. SMs revealed massive genomic alterations after aCGH analysis, including homozygous deletion of CDKN2A/2B and amplification of ERBB2 containing region, whereas EMs showed less genomic alterations. Uromodulin was highly expressed in most of the cases. After 4-week treatment, iron deposition in the mesothelia was observed with 8-hydroxy-2 0 -deoxyguanosine formation. These results not only show two distinct molecular pathways for iron-induced peritoneal mesothelioma, but also support the hypothesis that oxidative stress by iron overload is a major cause of CDKN2A/2B homozygous deletion.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Akatsuka

Yamashita

et al. 2010

Laboratory Investigation

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“…The mechanism by which KBrO 3 induces thyroid tumors is not known but may involve a genotoxic mechanism through direct oxidant damage as KBrO 3 was found to be mutagenic in the Ames test and to cause chromosomal aberrations in Chinese hamsterbroblasts (23). After 12 weeks (84 days) of treatment, serum T 3 concentrations were decreased in a treatment-dependent manner but serum T 4 concentrations were unaffected (47). Serum TSH levels were not measured, so it is dif cult to ascertain from this study if KBrO 3 induces thyroid tumors by a nonhormonal mechanism.…”

Section: Histopathologymentioning

confidence: 99%

Subchronic Sodium Chlorate Exposure in Drinking Water Results in a Concentration-Dependent Increase in Rat Thyroid Follicular Cell Hyperplasia

et al. 2001

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Chlorine dioxide (ClO 2 ) is an effective drinking water disinfectant, but sodium chlorate (NaClO 3 ) has been identi ed as a potentially harmful disinfection by-product . Studies were performed to describe the developmen t of thyroid lesions in animals exposed to NaClO 3 in the drinking water. Male and female F344 rats and B6C3F 1 mice were exposed to 0, 0.125, 0.25, 0.5, 1.0, or 2.0 g/L NaClO 3 for 21 days. Additional male F344 rats were exposed to 0, 0.001, 0.01, 0.1, 1.0, or 2.0 g/L NaClO 3 for 90 days. Female F344 rats were exposed to 0, 0.5, 1.0, 2.0, 4.0, or 6.0 g/L of NaClO 3 for 105 days. Thyroid tissues were processed by routine methods for light microscopi c examination, and follicular cell hyperplasia was diagnosed using a novel method. Thyroid hormone levels were altered signi cantly after 4 and 21 days. NaClO 3 treatment induced a concentration-dependen t increase in the incidence and severity of thyroid follicular cell hyperplasia. Male rats are more sensitive to the effects of NaClO 3 treatment than females. Follicular cell hyperplasi a was not present in male or female B6C3F 1 mice. These data can be used to estimate the human health risk that would be associated with using ClO 2 , rather than chlorine, to disinfect drinking water.

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“…Bromine has been shown to be carcinogenic in rats, hamsters and mice. 48,[60][61][62][63] Additionally, its mutagenic effects in several in vitro [64][65][66] and in vivo 67,68 test systems have been verified. The mechanisms underlying the genotoxicity of bromine are only partially understood.…”

Section: Cell Viability and Comet Assaymentioning

confidence: 88%

Synthesis, DNA Interaction and Genotoxic Evaluation of a Photoactive Benzothiadiazole with Potential Application in Photovoltaic Paint

Damiani¹,

Rohr²,

Westrup³

et al. 2017

J. Braz. Chem. Soc.

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A new fluorophore containing 2,1,3-benzothiadiazole unit with alkylated tetrazole terminal groups as electron donors connected through a π-conjugated system of the type (D-π-A-π-D) was synthesized using the Sonogashira coupling reaction with good yields. The genotoxicity of the two intermediate compounds and the final product was evaluated in vitro in consideration of the potential application of the new compound in the chemical production of photovoltaic paints. The new fluorophore did not show significant biological effects in the cell viability test and the comet assay when compared with the intermediate compounds that were obtained synthetically despite the ability to interact with deoxyribonucleic acid (DNA) as demonstrated in circular dichroism assays. Thus, the compound does not show toxic or genotoxic activity, and therefore, it can be applied as a pigment in photovoltaic paint.

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Time- and Dose-Dependent Development of Potassium Bromate-Induced Tumors in Male Fischer 344 Rats

Cited by 60 publications

References 20 publications

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Subchronic Sodium Chlorate Exposure in Drinking Water Results in a Concentration-Dependent Increase in Rat Thyroid Follicular Cell Hyperplasia

Synthesis, DNA Interaction and Genotoxic Evaluation of a Photoactive Benzothiadiazole with Potential Application in Photovoltaic Paint

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