Carcinogenic 3-nitrobenzanthrone but not 2-nitrobenzanthrone is metabolised to an unusual mercapturic acid in rats

Linhart, Igor; Mráz, Jaroslav; Hanzlíková, Iveta; Silhankova, A.; Frantík, E; Himl, Michal

doi:10.1016/j.toxlet.2011.11.017

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…Despite the fact 2-NBA has been more abundantly found in airborne samples, screening assays studies suggest the genotoxic potency of 2-NBA is significantly lower than 3-NBA 34–36 . Both of them are lipophilic substances (K ow = 3.99 for 2-NBA and K ow = 3.90 for 3-NBA) yet they may be considered persistent in the environment 30 and may be transferred from atmosphere to other environmental compartments by wet or dry deposition.…”

Section: Introductionmentioning

confidence: 99%

Occurrence of the potent mutagens 2- nitrobenzanthrone and 3-nitrobenzanthrone in fine airborne particles

Santos

Rocha

Andrade

2019

Sci Rep

12,672

435

8,322

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Polycyclic aromatic compounds (PACs) are known due to their mutagenic activity. Among them, 2-nitrobenzanthrone (2-NBA) and 3-nitrobenzanthrone (3-NBA) are considered as two of the most potent mutagens found in atmospheric particles. In the present study 2-NBA, 3-NBA and selected PAHs and Nitro-PAHs were determined in fine particle samples (PM 2.5) collected in a bus station and an outdoor site. The fuel used by buses was a diesel-biodiesel (96:4) blend and light-duty vehicles run with any ethanol-to-gasoline proportion. The concentrations of 2-NBA and 3-NBA were, on average, under 14.8 µg g−1 and 4.39 µg g−1, respectively. In order to access the main sources and formation routes of these compounds, we performed ternary correlations and multivariate statistical analyses. The main sources for the studied compounds in the bus station were diesel/biodiesel exhaust followed by floor resuspension. In the coastal site, vehicular emission, photochemical formation and wood combustion were the main sources for 2-NBA and 3-NBA as well as the other PACs. Incremental lifetime cancer risk (ILCR) were calculated for both places, which presented low values, showing low cancer risk incidence although the ILCR values for the bus station were around 2.5 times higher than the ILCR from the coastal site.

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Section: Introductionmentioning

confidence: 99%

Occurrence of the potent mutagens 2- nitrobenzanthrone and 3-nitrobenzanthrone in fine airborne particles

Santos

Rocha

Andrade

2019

Sci Rep

12,672

435

8,322

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“…Indeed, aminoarylcysteine adducts were recently identified in globin of rats dosed with 3-nitrobenzanthrone, 1- and 2-naphthylamine, and aristolochic acid . Additionally, aminoarylmercapturic acids formed both via glutathione conjugation with arylnitrenium ions and via in vivo cleavage of the above-mentioned aminoarylcysteine globin adducts were identified in rat urine. , Some of these adducts and/or their in vivo cleavage products have been proposed as possible new biomarkers of cumulative exposure and effective dose of arylamines and nitroarenes . Thus, in the present work, we addressed the formation of analogous adducts also in globin and urine of rats dosed with 4-ABP, an important tobacco smoke carcinogen.…”

Section: Introductionmentioning

confidence: 99%

New Aminobiphenylcysteine Derivatives in Globin and Urine of Rats Dosed with 4-Aminobiphenyl, a Tobacco Smoke Carcinogen

Linhart

Hanzlíková

Mráz

et al. 2023

Chem. Res. Toxicol.

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The 4-biphenylnitrenium ion (BPN), a reactive metabolic intermediate of the tobacco smoke carcinogen 4-aminobiphenyl (4-ABP), can react with nucleophilic sulfanyl groups in glutathione (GSH) as well as in proteins. The main site of attack of these S-nucleophiles was predicted using simple orientational rules of aromatic nucleophilic substitution. Thereafter, a series of presumptive 4-ABP metabolites and adducts with cysteine were synthesized, namely, S-(4-amino-3-biphenyl)cysteine (ABPC), N-acetyl-S-(4amino-3-biphenyl)cysteine (4-amino-3-biphenylmercapturic acid, ABPMA), S-(4-acetamido-3-biphenyl)cysteine (AcABPC), and N-acetyl-S-(4-acetamido-3-biphenyl)cysteine (4-acetamido-3-biphenylmercapturic acid, AcABP-MA). Then, globin and urine of rats dosed with a single ip dose of 4-ABP (27 mg/kg b.w.) was analyzed by HPLC-ESI-MS 2 . ABPC was identified in acidhydrolyzed globin at levels of 3.52 ± 0.50, 2.74 ± 0.51, and 1.25 ± 0.12 nmol/g globin (mean ± S.D.; n = 6) on days 1, 3, and 8 after dosing, respectively. In the urine collected on day 1 (0−24 h) after dosing, excretion of ABPMA, AcABPMA, and AcABPC amounted to 1.97 ± 0.88, 3.09 ± 0.75, and 3.69 ± 1.49 nmol/kg b.w. (mean ± S.D.; n = 6), respectively. On day 2, excretion of the metabolites decreased by one order of magnitude followed by a slower decrease on day 8. Regarding the possible formation of AcABPC from ABPC, N-acetylation of the amino group at the biphenyl moiety prior to that at cysteine appears to be very unlikely. Thus, the structure of AcABPC indicates the involvement of N-acetyl-4-biphenylnitrenium ion (AcBPN) and/or its reactive ester precursors in in vivo reactions with GSH and protein-bound cysteine. ABPC in globin might become an alternative biomarker of the dose of toxicologically relevant metabolic intermediates of 4-ABP.

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“…

per nanomole in the Ames test to date. In this way, 3-NBA, a nitroketone polycyclic aromatic compound, has attracted much attention from the scientific community due to its genotoxic and mutagenic potential even if present in extremely small quantities in diesel exhaust particles [22][23][24][25][26] .Although the occurrence of traditional PAHs and other petroleum-related substances in abiotic compartments of marine environments have been subject of several studies 6,27-30 , much less attention has been paid to the effects of these substances on living organisms, which some of them may be the base of the marine food chain (i.e. polychaetes).

…”

mentioning

confidence: 99%

“…per nanomole in the Ames test to date. In this way, 3-NBA, a nitroketone polycyclic aromatic compound, has attracted much attention from the scientific community due to its genotoxic and mutagenic potential even if present in extremely small quantities in diesel exhaust particles [22][23][24][25][26] .…”

mentioning

confidence: 99%

Occurrence of 3-nitrobenzanthrone and other powerful mutagenic polycyclic aromatic compounds in living organisms: polychaetes

Sola

Santos

Martinez

et al. 2020

Sci Rep

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In this work we report the occurrence of powerful mutagenic 3-nitrobenzanthrone (3-NBA), in addition to 18 polycyclic aromatic hydrocarbons (PAHs), 6 oxygenated PAHs and 27 nitrated PAHs in polychaete worms. Benzanthrone (BA), another important mutagenic polycyclic aromatic compound (PAC) also was detected in the samples. Polychaete annelids have great ecological relevance, being widely distributed in different environmental conditions, from intertidal zones up to seven thousand feet deep areas. They are abundantly found in both contaminated and uncontaminated areas and, therefore, used as indicators of the pollution status of a given area. As we know, so far, most of these PACs has not been previously reported in living organisms before. The 3-NBA concentrations determined in this study were within 0.11–5.18 µg g−1. Other relevant PACs such as PAHs, quinones and nitro-PAHs were found in maximum concentrations at 0.013 µg g−1 (coronene) to 11.1 µg g−1 (benzo[k]fluoranthene), 0.823 µg g−1 (9,10-phenenthrenequinone) to 12.1 µg g−1 (1,4-benzoquinone) and 0.434 (1-nitronaphthalene) µg g−1 to 19.2 µg g−1 (6-nitrobenzo[a]pyrene), respectively. Principal component analysis (PCA), ternary correlations and diagnostic ratios were employed in order to propose probable sources for PACs. Although statistical analysis preliminarily has indicated both pyrogenic and petrogenic contributions, petrogenic sources were predominant reflecting the impacts of petroleum exploration and intensive traffic of boats in the study area.

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Carcinogenic 3-nitrobenzanthrone but not 2-nitrobenzanthrone is metabolised to an unusual mercapturic acid in rats

Cited by 8 publications

References 32 publications

Occurrence of the potent mutagens 2- nitrobenzanthrone and 3-nitrobenzanthrone in fine airborne particles

Occurrence of the potent mutagens 2- nitrobenzanthrone and 3-nitrobenzanthrone in fine airborne particles

New Aminobiphenylcysteine Derivatives in Globin and Urine of Rats Dosed with 4-Aminobiphenyl, a Tobacco Smoke Carcinogen

Occurrence of 3-nitrobenzanthrone and other powerful mutagenic polycyclic aromatic compounds in living organisms: polychaetes

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