Phenylguanine Found in Urine after Benzene Exposure

Norpoth, K.; Müller, Günther; Schell, Christoph; Jorg, E

doi:10.2307/3433157

Cited by 5 publications

(2 citation statements)

References 19 publications

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“…When Norpoth et al detected in urine of rats dosed with benzene a compound co-eluting with and showing similar UV spectrum as authentic 7-phenylguanine (7-PhG), it seemed that 7-PhG could find application as a molecular dosimeter of both exposure and DNA damage by benzene (Norpoth et al, 1988;Schell et al, 1993). However, this finding was later disproved by the same group, when urinary 7-PhG could not be confirmed by more sensitive methods, such as ELISA and FIA using specific monoclonal antibodies (Norpoth et al, 1996). The authors concluded that compound(s) slightly different from 7-PhG, possibly containing a hydroxy function, were excreted as guanine adduct(s) of benzene (Schell et al, 1993).…”

Section: Introductionmentioning

confidence: 92%

Reactions of benzene oxide, a reactive metabolite of benzene, with model nucleophiles and DNA

Míčová

Linhart

2012

Xenobiotica

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1. Reactivity of benzene oxide (BO), a reactive metabolite of benzene, was studied in model reactions with biologically relevant S- and N-nucleophiles by LC-ESI-MS. 2. Reaction with N-acetylcysteine (NAC) in aqueous buffer solutions gave N-acetyl-S-(6-hydroxycyclohexa-2,4-dien-1-yl)cysteine (pre-phenylmercapturic acid, PPhMA), which was easily dehydrated in acidic solutions to phenylmercapturic acid (PhMA). The yield of PPhMA + PhMA increased exponentially with pH up to 11% in the pH range from 5.5 to 11.4. 3. Primary 6-hydroxycyclohexa-2,4-dien-1-yl (HC) adducts were detected also in reactions of purine nucleosides and nucleotides under physiological conditions. After a vigorous acidic hydrolysis, all HC adducts were converted to corresponding phenyl purines, which were identified as 7-phenylguanine (7-PhG), 3-phenyladenine (3-PhA) and N(6)-phenyladenine (6-PhA). The yield of 7-PhG amounted to 14 ± 5 and 16 ± 7 ppm for 2'-deoxyguanosine and 2'-deoxyguanosine-5'-monophosphate, respectively, that of 6-PhA was 500 ± 70 and 455 ± 75 ppm with 2'-deoxyadenosine and 2'-deoxyadenosine-5'-phosphate, respectively, with only traces of 3-PhA. 4. Reactions with the DNA followed by acidic hydrolysis yielded 26 ± 11 ppm (mean ± SD; n = 9) of 7-PhG as the sole adduct detected. 5. In contrast to the reactions with S-nucleophiles, the reactivity of BO with nucleophilic sites in the DNA is very low and can therefore hardly account for a significant DNA damage caused by benzene.

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Section: Introductionmentioning

confidence: 92%

Reactions of benzene oxide, a reactive metabolite of benzene, with model nucleophiles and DNA

Míčová

Linhart

2012

Xenobiotica

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“…A N-7-fenilguanina pode ser determinada na urina por HPLC-UV após pré-tratamento da amostra empregando cromatografia de íons e extração em fase sólida. Apesar da determinação ser específica e estar diretamente ligada à carcinogenicidade do benzeno, a sensibilidade do método analítico não permite avaliações de exposição à concentrações inferiores à 5 ppm (16 mg.m -3 ) de benzeno no ar [44][45] . Nos últimos anos, os ácidos trans,trans-mucônico (AM) e S-fenilmercaptúrico (AFM) têm sido determinados na urina como IBEs.…”

Section: Figura 1 Esquema Do Metabolismo Do Benzenounclassified

Avaliação dos métodos analíticos para a determinação de metabólitos do benzeno como potenciais biomarcadores de exposição humana ao benzeno no ar

Coutrim¹,

Carvalho²,

Arcuri³

2000

Quím. Nova

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EVALUATION OF THE ANALYTICAL METHODS TO DETERMINATE BENZENE METABO-LITES AS POTENCIAL BIOMARKERS FOR DETERMINING HUMAN EXPOSURE TO BEN-ZENE IN AIR.Increasing attention is being paid to the use of biomarkers for determining the exposure of humans to air toxics. Biomarkers include the nonreacted toxic substance, their metabolites, or the reaction products of these toxics with naturally substances in the body. Significant progress has been made in the measurement of biomarkers during the past several years. Much of this progress has been because of the development of advanced analytical techniques for identification and quantification of the chemical species in complex matrix, such as biological fluids. The assessment of the potential cancer risk associated with exposure to benzene at occupational and non-occupational ambient is necessary because of the toxicological implications of this air pollutant. Thus, in this review, the analytical methodologies used to determine the benzene metabolites, in special, urinary muconic acid and S-phenylmercapturic acid, are described and several problems affecting the precision of these procedures are discussed. Finally, in view of the difficulty pointed out for selecting the more adequate biomarker, further studies to evaluate the human exposure levels to benzene should be done.Keywords: human exposure to air benzene; biomarkers; muconic acid determination; S-phenylmercapturic acid determination. REVISÃO INTRODUÇÃOO benzeno, um composto reconhecidamente carcinogênico, é uma substância onipresente na atmosfera devido às contribuições de emissões biogênicas e principalmente antropogêni-cas. Para algumas emissões antropogênicas, aquelas provenientes de indústrias que produzem ou manuseiam o benzeno, o controle deste poluente tem sido feito regularmente, entretanto, para outras não se têm o conhecimento de suas concentrações e implicações ambientais. Estima-se que mundialmente cerca de dois milhões de trabalhadores estejam expostos ocupacionalmente ao benzeno a cada ano 1 . Contudo, estratégias para reduzir o nível de exposição têm sido feitas para assegurar uma melhoria na qualidade de vida desses trabalhadores, como a melhoria de tecnologia dos meios de produção, a pressão das políticas de vigilância à saúde ocupacional, a tendên-cia mundial de substituição do benzeno como solvente nos processos industriais e o avanço tecnológico para a determinação de espécies no ar em concentrações muito baixas. Por outro lado, o aumento gradativo da concentração de benzeno em atmosferas urbanas tem indicado que a exposição ao benzeno em ambientes não ocupacionais não pode ser desprezada. Apesar das concentrações de benzeno em ambientes ocupacionais atingirem níveis até 100 vezes maiores do que em outros ambientes 2 , a exposição ao benzeno não ocupacional deve merecer atenção especial por se tratar de composto genotóxico e consequentemente sem limite seguro de exposição 2,3

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3‐(3,4‐Dihydroxyphenyl)adenine, a urinary DNA adduct formed in mice exposed to high concentrations of benzene

Mikeš

Šístek

Krouželka

et al. 2012

J of Applied Toxicology

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Metabolism of benzene, an important environmental and industrial carcinogen, produces three electrophilic intermediates, namely, benzene oxide and 1,2- and 1,4-benzoquinone, capable of reacting with the DNA. Numerous DNA adducts formed by these metabolites in vitro have been reported in the literature, but only one of them was hitherto identified in vivo. In a search for urinary DNA adducts, specific LC-ESI-MS methods have been developed for the determination in urine of six nucleobase adducts, namely, 7-phenylguanine, 3-phenyladenine, 3-hydroxy-3,N(4) -benzethenocytosine, N(2) -(4-hydroxyphenyl)guanine, 7-(3,4-dihydroxyphenyl)guanine and 3-(3,4-dihydroxyphenyl)-adenine (DHPA), with detection limits of 200, 10, 260, 50, 400 and 200 pg ml(-1) , respectively. Mice were exposed to benzene vapors at concentrations of 900 and 1800 mg m(-3) , 6 h per day for 15 consecutive days. The only adduct detected in their urine was DHPA. It was found in eight out of 30 urine samples from the high-exposure group at concentrations of 352 ± 146 pg ml(-1) (mean ± SD; n = 8), whereas urines from the low-exposure group were negative. Assuming the DHPA concentration in the negative samples to be half of the detection limit, conversion of benzene to DHPA was estimated to 2.2 × 10(-6) % of the absorbed dose. Thus, despite the known high mutagenic and carcinogenic potential of benzene, only traces of a single DNA adduct in urine were detected. In conclusion, DHPA is an easily depurinating adduct, thus allowing indication of only high recent exposure to benzene, but not long-term damage to DNA in tissues.

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Phenylguanine Found in Urine after Benzene Exposure

Cited by 5 publications

References 19 publications

Reactions of benzene oxide, a reactive metabolite of benzene, with model nucleophiles and DNA

Reactions of benzene oxide, a reactive metabolite of benzene, with model nucleophiles and DNA

Avaliação dos métodos analíticos para a determinação de metabólitos do benzeno como potenciais biomarcadores de exposição humana ao benzeno no ar

3‐(3,4‐Dihydroxyphenyl)adenine, a urinary DNA adduct formed in mice exposed to high concentrations of benzene

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