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  • DNA adducts  (17)
  • 1
    Keywords: CANCER ; CELLS ; EXPRESSION ; IN-VIVO ; LUNG-CANCER ; DNA adducts ; RISK ; GENE ; LINES ; ACTIVATION ; DNA ; 3-aminobenzanthrone ; 3-nitrobenzanthrone ; AIR ; CARCINOGENESIS ; CYP1A2 ; CYTO-TOXIC METABOLITES ; DIESEL EXHAUST ; DNA ADDUCT FORMATION ; ENVIRONMENTAL CONTAMINANT 3-NITROBENZANTHRONE ; GENETIC POLYMORPHISMS ; HETEROCYCLIC AMINES ; HETEROLOGOUS EXPRESSION ; HUMAN CYTOSOLIC SULFOTRANSFERASES ; IONS ; metabolic activation ; NAT : SULT ; nitro-PAH ; P-32- postlabeling ; PHENOL SULFOTRANSFERASES ; POSTLABELING ANALYSIS
    Abstract: 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and ambient air pollution. 3-Aminobenzanthrone (3-ABA), 3- acetylaminobenzanthrone (3-Ac-ABA) and N-acetyl-N-hydroxy-3- aminobenzanthrone (N-Ac-N-OH-ABA) have been identified as 3-NBA metabolites. Recently we found that 3-NBA and its metabolites (3-ABA, 3-Ac-ABA and N-Ac-N-OH-ABA) form the same DNA adducts in vivo in rats. In order to investigate whether human cytochrome P450 (CYP) enzymes (i.e., CYPIA2), human N,O- acetyltransferases (NATs) and sulfotransferases (SULTs) contribute to the metabolic activation of 3-NBA and its metabolites we developed a panel of Chinese hamster V79MZ-hIA2 derived cell lines expressing human CYPIA2 in conjunction with human NATI, NAT2, SULTIAI or SULTIA2, respectively. Cells were treated with 0.01, 0.1 or I muM 3-NBA, or its metabolites (3- ABA, 3-Ac-ABA and N-Ac-N-OH-ABA). Using both enrichment versions of the P-32-postlabeling assay, nuclease P I digestion and butanol extraction, essentially 4 major and 2 minor DNA adducts were detected in the appropriate cell lines with all 4 compounds. The major ones were identical to those detected in rat tissue; the adducts lack an N-acetyl group. Human CYPIA2 was required for the metabolic activation of 3-ABA and 3-Ac-ABA (probably via N-oxidation) and enhanced the activity of 3-NBA (probably via nitroreduction). The lack of acetylated adducts suggests N-deacetylation of 3-Ac-ABA and N-Ac-N-OH-ABA. Thus, N-hydroxy-3-aminobenzanthrone (N-OH-ABA) appears to be a common intermediate for the formation of the electrophilic arylnitrenium ions capable of reacting with DNA. Human NAT I and NAT2 as well as human SULTIAI and SULTIA2 strongly contributed to the high genotoxicity of 3-NBA and its metabolites. Moreover, N,O-acetyltransfer reactions catalyzed by human NATs leading to the corresponding N-acetoxyester may be important in the bioactivation of N-Ac-N-OH-ABA. As human exposure to 3-NBA is likely to occur primarily via the respiratory tract, expression of CYPs, NATs and SULTs in respiratory tissues may contribute significantly and specifically to the metabolic activation of 3-NBA and its metabolites. Consequently, polymorphisms in these genes could be important determinants of lung cancer risk from 3-NBA
    Type of Publication: Journal article published
    PubMed ID: 12740904
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  • 2
    Keywords: BLOOD ; Germany ; LUNG ; DNA adducts ; EXPOSURE ; liver ; TISSUE ; HEART ; DNA ; kidney ; 3-nitrobenzanthrone ; DIESEL EXHAUST ; DNA ADDUCT FORMATION ; POSTLABELING ANALYSIS ; RAT ; BIOMARKERS ; CONTAMINANT 3-NITROBENZANTHRONE ; ENRICHMENT ; HPLC ; RATS ; METABOLITES ; HUMANS ; URINARY-BLADDER ; HUMAN ACETYLTRANSFERASES ; METABOLIC-ACTIVATION ; NUCLEOTIDES ; POLLUTANT 3-NITROBENZANTHRONE ; ADDUCTS ; PERFORMANCE LIQUID-CHROMATOGRAPHY ; DNA-ADDUCTS ; SURFACE SOIL ; V79 CELLS ; SINGLE ; RE ; EMISSIONS ; CARCINOGEN ; ADDUCT ; biomarker ; MUTAGEN 3-NITROBENZANTHRONE ; DNA ADDUCT ; intratracheal instillation ; P-32-postlabeling
    Abstract: 3-Nitrobenzanthrone (3-NBA) is an environmental pollutant and suspected human carcinogen found in emissions from diesel and gasoline engines and on the surface of ambient air particulate matter; human exposure to 3-NBA is likely to occur primarily via the respiratory tract. In our study female Sprague Dawley rats were treated by intratracheal instillation with a single dose of 0.2 or 2 mg/kg body weight of 3-NBA. Using the butanol enrichment version of the P-32-postlabeling method, DNA adduct formation by 3-NBA 48 hr after intratracheal administration in different organs (lung, pancreas, kidney, urinary bladder, heart, small intestine and liver) and in blood was investigated. The same adduct pattern consisting of up to 5 DNA adduct spots was detected by thin layer chromatography in all tissues and blood and at both doses. Highest total adduct levels were found in lung and pancreas (350 +/- 139 and 620 +/- 370 adducts per 10(8) nucleotides for the high dose and 39 +/- 18 and 55 +/- 34 adducts per 10(8) nucleotides for the low dose, respectively) followed by kidney, urinary bladder, heart, small intestine and liver. Adduct levels were dose-dependent in all organs (approximately 10-fold difference between doses). It was demonstrated by high performance liquid chromatography (HPLC) that all 5 3-NBA-derived DNA adducts formed in rats after intratracheal instillation are identical to those formed by other routes of application and are, as previously shown, formed from reductive metabolites bound to purine bases. Although total adduct levels in the blood were much lower (41 +/- 27 and 9.5 +/- 1.9 adducts per 10(8) nucleotides for the high and low dose, respectively) than those found in the lung, they were related to dose and to the levels found in lung. These results show that uptake of 3-NBA by the lung induces high levels of specific DNA adducts in several organs of the rat and an identical adduct pattern in DNA from blood. Therefore, 3-NBA-DNA adducts present in the blood are useful biomarkers for exposure to 3-NBA and may help to assess the effective biological dose in humans exposed to it. (C) 2005 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15856450
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  • 3
    Keywords: SPECTRA ; CANCER ; CELLS ; CELL ; human ; DNA adducts ; EXPOSURE ; RISK ; GENE ; TISSUE ; PATIENT ; DNA ; MECHANISM ; CARCINOGENESIS ; DNA ADDUCT FORMATION ; RATS ; tumour ; ASSOCIATION ; ACID ; NUMBER ; MUTATION ; p53 ; MUTATIONS ; ADDUCTS ; INDIVIDUALS ; NEPHROPATHY ; mutagenesis ; CONSUMPTION ; aristolochic acid ; CHINESE HERBS NEPHROPATHY ; DNA-ADDUCTS ; RENAL-FAILURE ; molecular ; FEATURES ; ONCOLOGY ; MOLECULAR-MECHANISM ; RE ; PATTERN ; P53 GENE ; RAS GENE ; ADDUCT FORMATION ; development ; analysis ; DNA ADDUCT ; p53 mutation ; RISK-FACTOR ; SPECTRUM ; PREDICT ; aetiology ; COVALENT DNA ADDUCTION ; HUMAN P53 GENE ; OCHRATOXIN-A
    Abstract: Balkan endemic nephropathy (BEN) is found in certain rural areas of the Balkans and affects at least 25 000 inhabitants. Of the many hypotheses on BEN, the Aristolochia hypothesis has recently gained ground substantiated by the investigations on aristolochic acid nephropathy (AAN). On both clinical and morphological grounds, AAN is very similar to BEN. That exposure to aristolochic acid (AA) of individuals living in endemic areas through consumption of bread made with flour contaminated with seeds of Aristolochia clematitis is responsible for BEN is an old hypothesis, but one which is fully consistent with the unique epidemiologic features of BEN. Here, we propose an approach to investigate AA-induced mutagenesis in BEN that can provide molecular clues to the aetiology of its associated urothelial cancer. The molecular mechanism of AA-induced carcinogenesis demonstrates a strong association between DNA adduct formation, mutation pattern and tumour development. A clear link between urothelial tumours, p53 mutations and AA exposure should emerge as more tumour DNA from BEN patients from different endemic areas becomes available for mutation analysis. We predict that the observed p53 mutation spectrum will be dominated by AT -〉 TA transversion mutations as has already been demonstrated in the human p53 gene of immortalized cells after exposure to AAI and urothelial tumours from BEN patients in Croatia. Moreover, the detection of AA-specific DNA adducts in renal tissue of a number of BEN patients and individuals living in areas endemic for BEN in Croatia provides new evidence that chronic exposure to AA is a risk factor for BEN and its associated cancer
    Type of Publication: Journal article published
    PubMed ID: 17434925
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  • 4
    Keywords: IN-VITRO ; human ; IN-VIVO ; LUNG ; MODEL ; VITRO ; DNA adducts ; liver ; ENZYMES ; METABOLISM ; MICE ; ACTIVATION ; DNA ; kidney ; DNA ADDUCT FORMATION ; LIVER-MICROSOMES ; RAT ; P-32-postlabelling ; BINDING ; MOUSE ; PATTERNS ; DNA-BINDING ; METABOLIC-ACTIVATION ; OXIDATION ; cytochrome P450 ; AGENT ; BODIES ; PATTERN ; WEIGHT ; LEVEL ; pharmacology ; USA ; LOSSES ; PROSTAGLANDIN-H SYNTHASE ; anticancer drug ; ellipticine ; ENVIRONMENTAL-POLLUTANT 3-NITROBENZANTHRONE ; peroxidase ; DETERMINES SUSCEPTIBILITY ; XENOBIOTIC-METABOLISM
    Abstract: Ellipticine is an antineoplastic agent, which forms covalent DNA adducts mediated by cytochromes P450 (CYP) and peroxidases. We evaluated the role of hepatic versus extra-hepatic metabolism of ellipticine, using the HRN (Hepatic Cytochrome P450 Reductase Null) mouse model, in which cytochrome P450 oxidoreductase (POR) is deleted in hepatocytes, resulting in the loss of essentially all hepatic CYP function. HRN and wild-type (WT) mice were treated i.p. with 1 and 10 mg/kg body weight of ellipticine. Multiple ellipticine-DNA adducts detected by P-32-postlabelling were observed in organs from both mouse strains. Highest total DNA binding levels were found in liver, followed by lung, kidney, urinary bladder, colon and spleen. Ellipticine-DNA adduct levels in the liver of HRN mice were up to 65% lower relative to WT mice, confirming the importance of CYP enzymes for the activation of ellipticine in livers, recently shown in vitro with human and rat hepatic microsomes. When hepatic microsomes of both mouse strains were incubated with ellipticine, ellipticine-DNA adduct levels with WT microsomes were up to 2.9-fold higher than with those from HRN mice. The ratios of ellipticine-DNA adducts in extra-hepatic organs between HRN and WT mice of up to 4.7 suggest that these organs can activate ellipticine and that more ellipticine is available in the circulation. These results and the DNA adduct patterns found in vitro and in vivo demonstrate that both CYP1A or 3A and peroxidases participate in activation of ellipticine to reactive species forming DNA adducts in the mouse model used in this study. (c) 2007 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17976674
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  • 5
    Keywords: CANCER ; BLOOD ; LUNG ; FOLLOW-UP ; lung cancer ; LUNG-CANCER ; DNA adducts ; EXPOSURE ; RISK ; SAMPLE ; SAMPLES ; DNA ; CARCINOGENESIS ; AIR-POLLUTION ; BIOMARKERS ; ASSOCIATION ; NO ; HUMANS ; DIFFERENCE ; REPAIR ; meta-analysis ; BLADDER ; bladder cancer ; BLADDER-CANCER ; cancer risk ; DAMAGE ; LYMPHOCYTES ; DNA-DAMAGE ; ADDUCTS ; CARCINOGENS ; case-control studies ; HEALTHY ; SMOKERS ; WHITE BLOOD-CELLS ; ALVEOLAR MACROPHAGES ; DNA-ADDUCTS ; ONCOLOGY ; case-control study ; INCREASE ; CARCINOGEN ; prospective studies ; LIFE ; METAANALYSIS ; LEVEL ; biomarker ; analysis ; DNA damage ; pooled analysis ; prospective ; prospective study ; ONSET ; COMPOUND ; CANCERS ; CANCER-RISK ; ENGLAND ; PREDICT ; POOLED-ANALYSIS ; HEAVY SMOKERS
    Abstract: Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies. In the pooled analysis, a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% confidence interval 1-28%; using the weighted mean difference method, 0.15 SD, units higher adducts in cases than in controls). The association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association was detected. The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years
    Type of Publication: Journal article published
    PubMed ID: 18343884
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  • 6
  • 7
    Keywords: INHIBITOR ; IN-VIVO ; INHIBITION ; LUNG ; LUNG-CANCER ; DNA adducts ; liver ; ENZYMES ; TISSUE ; MICE ; ACTIVATION ; DNA ; kidney ; 3-nitrobenzanthrone ; CARCINOGENESIS ; DIESEL EXHAUST ; AIR-POLLUTION ; CONTAMINANT 3-NITROBENZANTHRONE ; BINDING ; DNA-BINDING ; METABOLIC-ACTIVATION ; ADDUCTS ; rodent ; DT-DIAPHORASE ; RAT-LIVER CYTOSOL ; XANTHINE-OXIDASE ; DNA-ADDUCTS ; V79 CELLS ; ACETYLTRANSFERASE ; ADDUCT ; COFACTOR ; CARCINOGENIC ARISTOLOCHIC ACIDS ; CYTOCHROME-P450 1A1 ; MUTAGEN 3-NITROBENZANTHRONE ; SULFOTRANSFERASES ; DNA ADDUCT ; sulfotransferase
    Abstract: 3-Nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one, 3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and air pollution. We compared the ability of human hepatic cytosolic samples to catalyze DNA adduct formation by 3-NBA. Using the (32)p-postlabeling method, we found that 12/12 hepatic cytosols activated 3-NBA to form multiple DNA adducts similar to those formed in vivo in rodents. By comparing 3-NBA-DNA adduct formation in the presence of cofactors of NAD(P)H:quinone oxidoreductase (NQO1) and xanthine oxidase, most of the reductive activation of 3-NBA in human hepatic cytosols was attributed to NQO1. Inhibition of adduct formation by dicoumarol, an NQO1 inhibitor, supported this finding and was confirmed with human recombinant NQO1. When cofactors of N,O-acetyltransferases (NAT) and sulfotransferases (SUIT) were added to cytosolic samples, 3-NBA-DNA adduct formation increased 10- to 35-fold. Using human recombinant NQO1 and NATs or SULTs, we found that mainly NAT2, followed by SULT1A2, NAT1, and, to a lesser extent, SULT1A1 activate 3-NBA. We also evaluated the role of hepatic NADPH:cytochrome P450 oxidoreductase (POR) in the activation of 3-NBA in vivo by treating hepatic POR-null mice and wild-type littermates i.p. with 0.2 or 2 mg/kg body weight of 3-NBA. No difference in DNA binding was found in any tissue examined (liver, lung, kidney, bladder, and colon) between null and wild-type mice, indicating that 3-NBA is predominantly activated by cytosolic nitroreductases rather than microsomal POR. Collectively, these results show the role of human hepatic NQO1 to reduce 3-NBA to species being further activated by NATs and SULTs
    Type of Publication: Journal article published
    PubMed ID: 15805261
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  • 8
    Keywords: CANCER ; CELLS ; EXPRESSION ; INHIBITOR ; IN-VIVO ; INHIBITION ; LUNG-CANCER ; DNA adducts ; SAMPLES ; TIME ; ACTIVATION ; DNA ; 3-nitrobenzanthrone ; AIR ; CARCINOGENESIS ; DIESEL EXHAUST ; DNA ADDUCT FORMATION ; ENVIRONMENTAL CONTAMINANT 3-NITROBENZANTHRONE ; metabolic activation ; AIR-POLLUTION ; INDUCTION ; LIVER-MICROSOMES ; P-450 REDUCTASE ; RAT ; SUDAN-I
    Abstract: Determining the capability of humans to metabolize the suspected carcinogen 3-nitrobenzanthrone (3-NBA) and understanding which human enzymes are involved in its activation are important in the assessment of individual susceptibility to this environmental contaminant found in diesel exhaust and ambient air pollution. We compared the ability of eight human hepatic microsomal samples to catalyze DNA adduct formation by 3-NBA. Using two enrichment procedures of the P-32-postlabeling method, nuclease P1 digestion and butanol extraction, we found that all hepatic microsomes were competent to activate 3-NBA. DNA adduct patterns with multiple adducts, qualitatively similar to those found recently in vivo in rats, were observed. Additionally one major DNA adduct generated by human microsomes was detected. The role of specific cytochromes P450 (P450) and NADPH:P450 reductase in the human hepatic microsomal samples in 3-NBA activation was investigated by correlating the P450- and NADPH:P450 reductase- linked catalytic activities in each microsomal sample with the level of DNA adducts formed by the same microsomes. On the basis of this analysis, most of the hepatic microsomal activation of 3-NBA was attributed to NADPH:P450 reductase. Inhibition of DNA adduct formation in human liver microsomes by a-lipoic acid, an inhibitor of NADPH:P450 reductase, supported this finding. Using the purified rabbit enzyme and recombinant human NADPH:P450 reductase expressed in Chinese hamster V79 cells, we confirmed the participation of this enzyme in the formation of 3-NBA-derived DNA adducts. Moreover, essentially the same DNA adduct pattern found in microsomes was detected in metabolically competent human lymphoblastoid MCL-5 cells. The role of individual human recombinant P450s 1A1, 1A2, 1B1, 2A6, 2B6, 2D6, 2C9, 2E1, and 3A4 and of NADPH:P450 reductase in the metabolic activation of 3-NBA, catalyzing DNA adduct formation, was also examined using microsomes of baculovirus-transfected insect cells containing the recombinant enzymes (Supersomes). DNA adducts were observed in all Supersomes preparations, essentially similar to those found with human hepatic microsomes and in human cells. Of all of the recombinant human P450s, P450 2B6 and -2D6 were the most efficient to activate 3- NBA, followed by P450 1A1 and -1A2. These results demonstrate for the first time the potential of human NADPH:P450 reductase and recombinant P450s to contribute to the metabolic activation of 3-NBA by nitroreduction
    Type of Publication: Journal article published
    PubMed ID: 12782579
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  • 9
    Keywords: CELLS ; IN-VITRO ; human ; IN-VIVO ; LUNG ; PATHWAYS ; VIVO ; DNA adducts ; EXPOSURE ; liver ; ENZYMES ; TISSUE ; HEART ; ACTIVATION ; DNA ; kidney ; 3-aminobenzanthrone ; 3-nitrobenzanthrone ; CARCINOGENESIS ; DIESEL EXHAUST ; DNA ADDUCT FORMATION ; metabolic activation ; nitro-PAH ; RAT ; animals ; AROMATIC-AMINES ; BASE ; BIOMARKERS ; BODY-WEIGHT ; colon ; CONTAMINANT 3-NITROBENZANTHRONE ; ENRICHMENT ; HPLC ; P-32-postlabelling ; RATS ; TISSUES ; tumour
    Abstract: Diesel exhaust is known to induce tumours in animals and is suspected of being carcinogenic in humans. Of the compounds found in diesel exhaust, 3-nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspected human carcinogen forming multiple DNA adducts in vitro. 3-Aminobenzanthrone (3-ABA). 3- acetylaminobenzanthrone (3-Ac-ABA), and N-acetyl-N-hydroxy-3- aminobenzanthrone (N-Ac-N-OH-ABA) were identified as 3-NBA metabolites. In order to gain insight into the pathways of metabolic activation leading to 3-NBA-derived DNA adducts we treated Wistar rats intraperitoneally with 2 mg/kg body weight of 3-NBA, 3-ABA. 3-Ac-ABA, or N-Ac-N-OH-ABA and compared DNA adducts present in different organs, With each compound either four or five DNA adduct spots were detected by TLC in all tissues examined (lung, liver. kidney, heart, pancreas, and colon) using the nuclease P1 or butanol enrichment version of the P-32-postlabelling method, respectively. Using HPLC co- chromatographic analysis we showed that all major 3-NBA-DNA adducts produced in vivo in rats are derived from reductive metabolites bound to purine bases and lack an N-acetyl group. Our results indicate that 3-NBA metabolites (3-ABA, 3-Ac-ABA and AT-Ac-N-OH-ABA) undergo several biotransformations and that N-hydroxy-3-aminobenzanthrone (N-OH-ABA) appears to be the common intermediate in 3-NBA-derived DNA adduct formation. Therefore, 3-NBA-DNA adducts are useful biomarkers for exposure to 3-NBA and its metabolites and may help to identify enzymes involved in their metabolic activation. (C) 2002 Elsevier Science (USA). All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 12480528
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  • 10
    Keywords: BLOOD ; Germany ; human ; LUNG ; LUNG-CANCER ; DNA adducts ; EXPOSURE ; liver ; LONG-TERM ; TISSUE ; HEART ; TIME ; DNA ; kidney ; 3-nitrobenzanthrone ; CARCINOGENESIS ; DIESEL EXHAUST ; ENVIRONMENTAL CONTAMINANT 3-NITROBENZANTHRONE ; RAT ; animals ; BIOMARKERS ; RATS ; TISSUES ; treatment ; TARGET ; HUMAN ACETYLTRANSFERASES ; METABOLIC-ACTIVATION ; POLYCYCLIC AROMATIC-HYDROCARBONS ; ADDUCTS ; BODY ; SMALL-INTESTINE ; DECLINE ; HIGH-LEVEL ; DNA-ADDUCTS ; V79 CELLS ; SINGLE ; ONCOLOGY ; LEVEL ; biomarker ; DNA ADDUCT ; PERSISTENCE ; LOSSES ; uptake ; correlation ; P-32-POSTLABELING ANALYSIS ; carcinogenic ; lungs ; animal ; LONG-TERM PERSISTENCE ; WHOLE-BLOOD ; CD-1 MICE
    Abstract: Sprague-Dawley rats were treated by intratracheal instillation with a single dose of 0.2 mg/kg body wt of 3-nitrobenzanthrone (3-NBA), and whole blood, lungs, pancreases, kidneys, urinary bladders, hearts, small intestines and livers were removed at various times after administration. At five posttreatment times (2 days, 2, 10, 20 and 36 weeks), DNA adducts were analysed in each tissue by P-32-postlabelling to study their long-term persistence. 3-NBA-derived DNA adducts consisting of the same adduct pattern were observed in all tissues from animals killed between 2 days and 36 weeks and between 2 days and 20 weeks in blood. DNA isolated from whole blood contained the same 3-NBA-specific adduct pattern as that found in tissues. Although total adduct levels in the blood were much lower than those found in the lung, the target organ of 3-NBA tumourigenicity, they were related (20-25%, R-2 = 0.98) to the levels found in lung. In all organs, total adduct levels decreased over time to 20-30% of the initial levels till the latest time point (36 weeks) and showed a biphasic profile, with a rapid loss during the first 2 weeks followed by a much slower decline that reached a stable plateau at 20 weeks after treatment. These results show that uptake of 3-NBA by the lung induces high levels of specific DNA adducts in target and non-target organs of the rat. The correlation between DNA adducts in lung and blood suggests that persistent 3-NBA-DNA adducts in the blood may be useful biomarkers for human respiratory exposure to 3-NBA
    Type of Publication: Journal article published
    PubMed ID: 17114646
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