NADPH-cytochrome P450 reductase-mediated denitration reaction of 2,4,6-trinitrotoluene to yield nitrite in mammals

Shinkai, Yasuhiro; Nishihara, Yuya; Amamiya, Masahiro; Wakayama, Toshihiko; Li, Song; Kikuchi, Tomohiro; Nakai, Yoshinobu; Shimojo, Naoki; Kumagai, Yoshito

doi:10.1016/j.freeradbiomed.2015.09.011

Cited by 11 publications

(2 citation statements)

References 42 publications

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“…An explanation for this discrepancy is that TNT may increase the production of NOx found in the serum through an alternative pathway. We suggest this because we recently found that NADPH-cytochrome P450 reductase catalyzes the reduction of TNT to form HADNT, resulting in denitration reaction through the interaction between TNT and HADNT to release nitrite (Shinkai et al, 2015b). It has previously been reported that nitrite can be reduced to NO through several pathways (Lundberg and Weitzberg, 2005;Shiva, 2013).…”

Section: Resultsmentioning

confidence: 90%

Health survey of workers in a 2,4,6-trinitrotoluene explosives factory in Fuxin, China

Shinkai

Kikuchi

et al. 2015

Fundam. Toxicol. Sci.

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-2,4,6-Trinitrotoluene (TNT) is a serious occupational and environmental pollutant. We conducted a cross-sectional health survey of workers in a TNT explosives factory in Fuxin, China. For each subject, we determined their blood pressure, hematotoxicity parameters, glutathione concentration, lipid hydroperoxide concentration, superoxide dismutase activity, and nitrite/nitrate (NOx) concentration in serum. Significantly fewer white blood cells were found in samples from male workers exposed to TNT than in samples from control male workers, but hematological parameters (such as the amount of hemoglobin present, the hematocrit value, and the formation of methemoglobin) varied little between the exposed and control workers. Exposure of male workers to TNT was found to cause their blood pressure to decrease significantly, concomitant with a tendency towards increased NOx concentrations in serum. On the other hand, lipid hydroperoxide (an oxidative stress marker) concentrations were significantly higher in female workers exposed to TNT than in control female workers. Our results suggest that TNT has different, deleterious effects in males and females, causing hematotoxic stress in males and oxidative stress in females.

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Section: Resultsmentioning

confidence: 90%

Health survey of workers in a 2,4,6-trinitrotoluene explosives factory in Fuxin, China

Shinkai

Kikuchi

et al. 2015

Fundam. Toxicol. Sci.

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“…The mechanisms underlying the toxicity and carcinogenicity of TNT and its metabolites are based on the induction of oxidative stress and reactive oxygen species (ROS) in biological tissues [20]. Another player in TNT mutagenicity could be the 4-hydroxylamino-2,6-dinitrotoluene (4-HADNT) intermediate, which is a product of cytochrome P450 catalysis on the way to 4-ADNT [21]. 4-HADNT has been shown to cause severe DNA damage to the male reproductive system in rats [22].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Trends for Blue Mussels from the German Environmental Specimen Bank Show First Evidence of Munition Contaminants Uptake

Strehse¹,

Bünning²,

Koschorreck

et al. 2023

Toxics

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Submerged munitions are present in marine waters across the globe. They contain energetic compounds (ECs), such as TNT and metabolites thereof, which are considered carcinogenic, exhibit toxic effects in marine organisms, and may affect human health. The aim of this study was to investigate the occurrence of ECs and their trends in blue mussels from the annual collections of the German Environmental Specimen Bank sampled over the last 30 years at three different locations along the coastline of the Baltic and North Sea. Samples were analyzed by GC-MS/MS for 1,3-dinitrobenzene (1,3-DNB), 2,4-dinitrotoluene (2,4-DNT), 2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2-ADNT), and 4-amino-2,6-dinitrotoluene (4-ADNT). The first signals indicating trace levels of 1,3-DNB were observed in samples from 1999 and 2000. ECs were also found below the limit of detection (LoD) in subsequent years. From 2012 onwards, signals just above the LoD were detected. The highest signal intensities of 2-ADNT and 4-ADNT, just below the LoQ (0.14 ng/g d.w. and 0.17 ng/g d.w., respectively), were measured in 2019 and 2020. This study clearly shows that corroding submerged munitions are gradually releasing ECs into the waters that can be detected in randomly sampled blue mussels, even though the concentrations measured are still in the non-quantifiable trace range.

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Phytodetoxification of TNT by transplastomic tobacco (Nicotiana tabacum) expressing a bacterial nitroreductase

et al. 2017

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Expression of the bacterial nitroreductase gene, nfsI, in tobacco plastids conferred the ability to detoxify TNT. The toxic pollutant 2,4,6-trinitrotoluene (TNT) is recalcitrant to degradation in the environment. Phytoremediation is a potentially low cost remediation technique that could be applied to soil contaminated with TNT; however, progress is hindered by the phytotoxicity of this compound. Previous studies have demonstrated that plants transformed with the bacterial nitroreductase gene, nfsI have increased ability to tolerate and detoxify TNT. It has been proposed that plants engineered to express nfsI could be used to remediate TNT on military ranges, but this could require steps to mitigate transgene flow to wild populations. To address this, we have developed nfsI transplastomic tobacco (Nicotiana tabacum L.) to reduce pollen-borne transgene flow. Here we have shown that when grown on solid or liquid media, the transplastomic tobacco expressing nfsI were significantly more tolerant to TNT, produced increased biomass and removed more TNT from the media than untransformed plants. Additionally, transplastomic plants expressing nfsI regenerated with high efficiency when grown on medium containing TNT, suggesting that nfsI and TNT could together be used to provide a selectable screen for plastid transformation.

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NADPH-cytochrome P450 reductase-mediated denitration reaction of 2,4,6-trinitrotoluene to yield nitrite in mammals

Cited by 11 publications

References 42 publications

Health survey of workers in a 2,4,6-trinitrotoluene explosives factory in Fuxin, China

Health survey of workers in a 2,4,6-trinitrotoluene explosives factory in Fuxin, China

Long-Term Trends for Blue Mussels from the German Environmental Specimen Bank Show First Evidence of Munition Contaminants Uptake

Phytodetoxification of TNT by transplastomic tobacco (Nicotiana tabacum) expressing a bacterial nitroreductase

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