Evaluation of cII mutations in lung of male Big Blue mice exposed by inhalation to vanadium pentoxide for up to 8 weeks

Manjanatha, Mugimane G.; Shelton, Sharon D.; Haber, Lynne T.; Gollapudi, B. Bhaskar; MacGregor, Judith A.; Rajendran, N.; Moore, Martha M.

doi:10.1016/j.mrgentox.2015.06.014

Cited by 13 publications

(11 citation statements)

References 24 publications

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“…Specifically, our study included a level of 1 mg/m 3 VP, which produced the maximal response in terms of induction of mouse lung tumors [3]. Evidence that this treatment had biological consequences was confirmed by the statistically significant increase in right lung weights of the 1 mg/m 3 exposed groups treated for 4 and 8 weeks [14], which is consistent with the expected inflammatory response to VP at this level. Finally, experience with the ACB-PCR approach suggests that the assay has sufficient sensitivity to detect early induction of mutation following carcinogen exposures.…”

Section: Discussionsupporting

confidence: 58%

“…No other clinical signs were observed and all animals survived the 4 and 8 week exposure periods. A statistically significant increase (P ≤ 0.05) in the lung weights was observed in the mice exposed to VP at the 1 mg/m 3 level after 4 and 8 weeks; however, no effect on lung weights was apparent in the 0.1 mg/m 3 animals at either time [14].…”

Section: Resultsmentioning

confidence: 83%

“…Consistent with the absence of induced 8-oxo-dG and induced Kras mutation, no significant increases in cII mutant frequency were noted in any of the VP-exposed treatment groups compared to controls. Lung cII mutant frequencies (×10 −6 ) in 0, 0.1, and 1.0 mg/m 3 VP treatment groups were 30, 39, and 24 in mice exposed for 4 weeks and 29, 48, and 17 in mice exposed for 8 weeks, respectively [14].…”

Section: Discussionmentioning

confidence: 94%

“…The milled test substance, V 2 O 5 (CAS # 1314-62-1; lot number H091608:62; purity 100%), a yellow powder, was supplied by EvrazStratcor, Inc. (Hot Springs, AR) along with a certificate of analysis which supported the characterization of the test substance. A compressed air operated Wright Dust Feeder Aerosol Generation system (BGI Incorporated, Waltham, MA) was used to generate respirable particulate aerosols of VP and the accuracy of the exposure conditions was confirmed analytically [14]. Male BB B 6 C 3 F 1 mice were purchased from BioReliance, Rockville, MD and supplied through Taconic Farms, Germantown, New York.…”

Section: Animals and Vp Exposurementioning

confidence: 99%

“…Male BB B 6 C 3 F 1 mice were purchased from BioReliance, Rockville, MD and supplied through Taconic Farms, Germantown, New York. After being acclimated to laboratory conditions for at least one week and acclimatized to the tubes over a 3-day period, 8-week-old male BB B 6 C 3 F 1 mice (6 mice/group) were exposed to target concentrations of 0.1 or 1.0 ppm VP or to sham filtered air by nose-only inhalation, 6 h/day, 5 days/week for 4 or 8 weeks [14]. The overall mean measured concentration levels of the test substance in the exposure chamber were 0.093 mg/m 3 and 1.178 mg/m 3 for the 4-week exposure period and 0.103 mg/m 3 and 1.041 mg/m 3 for the 8-week exposure period, corresponding to targeted concentrations of 0.1 and 1 mg/m 3 , respectively (personal communication, Dr. Narayanan Rajendran, Vice President and Manager Inhalation Division, Life Sciences Group, IIT Research Institute, Chicago, IL; [14]).…”

Section: Animals and Vp Exposurementioning

confidence: 99%

See 4 more Smart Citations

Quantification of Kras mutant fraction in the lung DNA of mice exposed to aerosolized particulate vanadium pentoxide by inhalation

Banda

McKim

Haber

et al. 2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Section: Discussionsupporting

confidence: 58%

Section: Resultsmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 94%

Section: Animals and Vp Exposurementioning

confidence: 99%

Section: Animals and Vp Exposurementioning

confidence: 99%

See 3 more Smart Citations

Quantification of Kras mutant fraction in the lung DNA of mice exposed to aerosolized particulate vanadium pentoxide by inhalation

Banda

McKim

Haber

et al. 2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

Self Cite

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Dose and temporal evaluation of ethylene oxide‐induced mutagenicity in the lungs of male big blue mice following inhalation exposure to carcinogenic concentrations

Manjanatha

Shelton

Chen

et al. 2017

Environ and Mol Mutagen

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Ethylene oxide (EO) is a direct acting alkylating agent; in vitro and in vivo studies indicate that it is both a mutagen and a carcinogen. However, it remains unclear whether the mode of action (MOA) for cancer for EO is a mutagenic MOA, specifically via point mutation. To investigate the MOA for EO-induced mouse lung tumors, male Big Blue (BB) B6C3F1 mice (10/group) were exposed to EO by inhalation, 6 hr/day, 5 days/week for 4 (0, 10, 50, 100, or 200 ppm EO), 8, or 12 weeks (0, 100, or 200 ppm EO). Lung DNA samples were analyzed for cII mutant frequency (MF) at 4, 8 and 12 weeks of exposure; the mutation spectrum was analyzed for mutants from control and 200 ppm EO treatments. Although EO-induced cII MFs were 1.5- to 2.7-fold higher than the concurrent controls at 4 weeks, statistically significant increases in the cII MF were found only after 8 and 12 weeks of exposure and only at 200 ppm EO (P ≤ 0.05), which is twice the highest concentration used in the cancer bioassay. Consistent with the positive response, DNA sequencing of cII mutants showed a significant shift in the mutational spectra between control and 200 ppm EO following 8 and 12 week exposures (P ≤ 0.035), but not at 4 weeks. Thus, EO mutagenic activity in vivo was relatively weak and required higher than tumorigenic concentrations and longer than 4 weeks exposure durations. These data do not follow the classical patterns for a MOA mediated by point mutations. Environ. Mol. Mutagen. 58:122-134, 2017. © 2017 Wiley Periodicals, Inc.

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Genotoxicity of 11 heavy metals detected as food contaminants in two human cell lines

Kopp

Zalko

Audebert

2017

Environ and Mol Mutagen

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Heavy metals, such as arsenic (As), antimony (Sb), barium (Ba), cadmium (Cd), cobalt (Co), germanium (Ge), lead (Pb), nickel (Ni), tellurium (Te), and vanadium (V) are widely distributed in the environment and in the food chain. Human exposure to heavy metals through water and food has been reported by different international agencies. Although some of these heavy metals are essential elements for human growth and development, they may also be toxic at low concentrations due to indirect mechanisms. In this study, the genotoxic and cytotoxic properties of 15 different oxidation statuses of 11 different heavy metals were investigated using high-throughput screening (γH2AX assay) in two human cell lines (HepG2 and LS-174T) representative of target organs (liver and colon) for food contaminants. Base on their lowest observed adverse effect concentration, the genotoxic potency of each heavy metal in each cell line was ranked in decreasing order, NaAsO > CdCl > PbCl (only in LS-174T cells) > As O > SbCl > K TeO > As O . No significant genotoxicity was observed with the other heavy metals tested. Cell viability data indicate that several heavy metals (As, Cd, Co, Ni, Sb, and Te) induce cytotoxicity at high concentrations, whereas an increase in the number of cells was observed for lead concentrations >100 µM in both cell lines tested, suggesting that lead stimulates cell growth. All these results highlight the possible human health hazards associated with the presence of heavy metals present in food. Environ. Mol. Mutagen. 59:202-210, 2018. © 2017 Wiley Periodicals, Inc.

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Evaluation of cII mutations in lung of male Big Blue mice exposed by inhalation to vanadium pentoxide for up to 8 weeks

Cited by 13 publications

References 24 publications

Quantification of Kras mutant fraction in the lung DNA of mice exposed to aerosolized particulate vanadium pentoxide by inhalation

Quantification of Kras mutant fraction in the lung DNA of mice exposed to aerosolized particulate vanadium pentoxide by inhalation

Dose and temporal evaluation of ethylene oxide‐induced mutagenicity in the lungs of male big blue mice following inhalation exposure to carcinogenic concentrations

Genotoxicity of 11 heavy metals detected as food contaminants in two human cell lines

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