Induction of rat liver γ-glutamyltranspeptidase-positive foci by oral administration of 1-nitropyrene

Denda, Ayumi; Tsutsumi, Masahiro; Tsujiuchi, Toshifumi; Eimoto, Hiroyuki; Konishi, Yoichi; Sato, Shigeaki

doi:10.1016/0304-3835(89)90031-1

Cited by 3 publications

(1 citation statement)

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“…The feasibility of detecting DNA and protein adducts of 1NP in purified DNA and protein was then extended to quantitate the adducts in the tissue-isolated DNA and protein samples obtained from rats that had been dosed with 30 and 100 mg/kg 1NP. The analyses detected both the DNA and protein adducts in all the analyzed organs (Figure A,B), with the highest levels being observed in the liver, followed by the large intestine, which was in good agreement with the previous observation that tumors were observed in the liver of 1NP-exposed rats. − The high levels of adducts in these two organs could be explained by the regional high enzymatic (reductase) activity. Because the liver is the organ responsible for xenobiotic metabolism and the large intestine is housed with anaerobic microbes that produce a high concentration of bacterial nitroreductase for the nitroreduction of 1NP, , it is reasonable that adducts were formed at high levels in these two organs.…”

Section: Resultssupporting

confidence: 89%

Quantification of DNA and Protein Adducts of 1-Nitropyrene: Significantly Higher Levels of Protein than DNA Adducts in the Internal Organs of 1-Nitropyrene Exposed Rats

Chan

Wong

2018

Chem. Res. Toxicol.

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1-Nitropyrene (1NP) level is closely associated with the mutagenicity of diesel exhaust and is being used as the marker molecule for diesel exhaust. Thus, quantitation of the exposure to 1NP may provide an efficient method for biomonitoring human exposure to diesel exhaust and risk assessment. Using ultra-performance liquid chromatography coupled with fluorescence or tandem mass spectrometric detection methods, we quantitated and compared in this study the DNA and protein adducts of 1NP in internal organs of 1NP-exposed rats. While previous studies using radioactivity-based detection methods were descriptive in nature and focused on the mutation-associated genetic materials, the results of our quantitative analysis showed, for the first time, a significantly higher concentration of the protein adduct than the DNA adduct in the tissue samples. The data also revealed higher in vivo stability of the protein adduct than that of the DNA adduct. Our results provide solid evidence that demonstrates that the protein adduct might be a more-sensitive dosimeter for 1-NP and, thus, diesel-exhaust exposure.

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Section: Resultssupporting

confidence: 89%

Quantification of DNA and Protein Adducts of 1-Nitropyrene: Significantly Higher Levels of Protein than DNA Adducts in the Internal Organs of 1-Nitropyrene Exposed Rats

Chan

Wong

2018

Chem. Res. Toxicol.

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Nitrogen Dioxide Exposure Activates γ-Glutamyl Transferase Gene Expression in Rat Lung

Takahashi

Oakes

Williams

et al. 1997

Toxicology and Applied Pharmacology

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The Role of Adrenocortical Hormones in the Regulation of Organism Response to Intratracheal Injections of Electrolysis Dust to Wistar Rats

Khripach

Knyazeva

Zheleznyak

et al. 2019

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Introduction. Adrenocortical hormones play a leading role in the adaptation of human organism to damaging factors. The aim of this study is to compare levels of cortisol and biochemical markers of organism damage (MOD) in blood samples of rats under a model of electrolysis dust (ED) inhalation exposure. ED being component of emissions in aluminum production and has high content of resinous substances (RS), including 3,4-benzpyrene. Material and methods. Male Wistar rats were injected ED intratracheally once per month, in doses corresponding to keeping of animals at ED concentrations of 1.0; 5.2 and 25.1 mg/m3, calculated on RS mass. 2 weeks after the 1st and 2nd ED administration and 6 days after the 3rd one, blood serum samples were used for determination of cortisol levels (ELISA) and the following 6 MOD: the intensity of luminol-enchanced chemiluminescence, activities of catalase, N-acetyl-β-D-glucosaminidase (NAG), acid DNAse, acetylesterase and γ-glutamyl transferase (GGT). Results. 2 weeks after the 1st and 2nd ED administrations (cortisol content 2 times reduced or not changed), similar significant changes were observed in almost all MOD; 2nd experimental point, if comparing with 1st point, had slight increase in oxidative stress and significant rise in GGT activity (a marker of precancer changes) at the maximum dose. On the contrary, 6 days after the 3rd injection of ED, in parallel with the increase of cortisol content in rat blood by 1.5 - 2 times, small significant changes were found for only one marker (NAG). The obtained data fit into existing concepts about protective role of cortisol and biphasic nature of its release into the blood, allow us to consider the absence of MOD, in parallel with rising levels of C, as a transit phase and have common problem aspects with CIRCI syndrome (Critical illness-Related Corticosteroid Insufficiency) in emergency medicine. Conclusion. Determination of cortisol levels by ELISA assay can be easily incorporated into any toxicological protocol as index of organism adaptive response, but further investigations are needed to clarify its characteristics and to build continuous model from separate time-dose points.

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Induction of rat liver γ-glutamyltranspeptidase-positive foci by oral administration of 1-nitropyrene

Cited by 3 publications

References 29 publications

Quantification of DNA and Protein Adducts of 1-Nitropyrene: Significantly Higher Levels of Protein than DNA Adducts in the Internal Organs of 1-Nitropyrene Exposed Rats

Quantification of DNA and Protein Adducts of 1-Nitropyrene: Significantly Higher Levels of Protein than DNA Adducts in the Internal Organs of 1-Nitropyrene Exposed Rats

Nitrogen Dioxide Exposure Activates γ-Glutamyl Transferase Gene Expression in Rat Lung

The Role of Adrenocortical Hormones in the Regulation of Organism Response to Intratracheal Injections of Electrolysis Dust to Wistar Rats

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