3-aminobenzanthrone, a human metabolite of the carcinogenic environmental pollutant 3-nitrobenzanthrone, induces biotransformation enzymes in rat kidney and lung.

4.00
Hdl Handle:
http://hdl.handle.net/10146/113104
Title:
3-aminobenzanthrone, a human metabolite of the carcinogenic environmental pollutant 3-nitrobenzanthrone, induces biotransformation enzymes in rat kidney and lung.
Authors:
Stiborova, Marie; Dracinska, Helena; Martinkova, Marketa; Mizerovska, Jana; Hudecek, Jiri; Hodek, Petr; Liberda, Jiri; Frei, Eva; Schmeiser, Heinz H.; Phillips, David H.; Arlt, Volker M.
Abstract:
3-aminobenzanthrone (3-ABA) is the metabolite of the carcinogenic air pollutant 3-nitrobenzanthrone (3-NBA). 3-ABA was investigated for its ability to induce cytochrome P450 1A1 (CYP1A1) and NAD(P)H:quinone oxidoreductase (NQO1) in kidney and lung of rats, and for the influence of such induction on DNA adduct formation by 3-ABA and 3-NBA. NQO1 is the enzyme that reduces 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize 3-ABA to the same intermediate. When activated by cytosolic and and/or microsomal fractions isolated from rat lung, the target organ for 3-NBA carcinogenicity, and kidney, both compounds generated the same DNA-adduct pattern, consisting of five adducts. When pulmonary cytosols isolated from rats that had been treated i.p. with 40 mg/kg bw of 3-ABA were incubated with 3-NBA, DNA adduct formation was up to 1.7-fold higher than in incubations with cytosols from control animals. This increase corresponded to an increase in protein level and enzymatic activity of NQO1. In contrast, no induction of NQO1 expression by 3-ABA treatment was found in the kidney. Incubations of 3-ABA with renal and pulmonary microsomes of 3-ABA-treated rats led to an increase of up to a 4.5-fold in DNA-adduct formation relative to controls. The stimulation of DNA-adduct formation correlated with a higher protein expression and activity of CYP1A1 induced by 3-ABA. These results show that by inducing lung and kidney CYP1A1 and NQO1, 3-ABA increases its own enzymatic activation as well as that of the environmental pollutant, 3-NBA, thereby enhancing the genotoxic and carcinogenic potential of both compounds.
Citation:
Mutat. Res. 2009, 676 (1-2):93-101
Journal:
Mutation Research
Issue Date:
31-May-2009
URI:
http://hdl.handle.net/10146/113104
DOI:
10.1016/j.mrgentox.2009.04.013
PubMed ID:
19398038
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2D-4W6XW3R-1&_user=1843694&_coverDate=05%2F31%2F2009&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=dd9e0a0a588c5ae02662c8617c839eb8&searchtype=a
Type:
Article
Language:
en
ISSN:
0027-5107
Sponsors:
This work was supported in part by the Grant Agency of the Czech Republic, grant 203/06/0329, the Ministry of Education of the Czech Republic, grants MSM0021620808 and 1M0505, the German Cancer Research Center and by Cancer Research UK. V.M. Arlt and D.H. Phillips are partners of ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943).
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorStiborova, Marieen
dc.contributor.authorDracinska, Helenaen
dc.contributor.authorMartinkova, Marketaen
dc.contributor.authorMizerovska, Janaen
dc.contributor.authorHudecek, Jirien
dc.contributor.authorHodek, Petren
dc.contributor.authorLiberda, Jirien
dc.contributor.authorFrei, Evaen
dc.contributor.authorSchmeiser, Heinz H.en
dc.contributor.authorPhillips, David H.en
dc.contributor.authorArlt, Volker M.en
dc.date.accessioned2010-10-18T08:11:28Z-
dc.date.available2010-10-18T08:11:28Z-
dc.date.issued2009-05-31-
dc.identifier.citationMutat. Res. 2009, 676 (1-2):93-101en
dc.identifier.issn0027-5107-
dc.identifier.pmid19398038-
dc.identifier.doi10.1016/j.mrgentox.2009.04.013-
dc.identifier.urihttp://hdl.handle.net/10146/113104-
dc.description.abstract3-aminobenzanthrone (3-ABA) is the metabolite of the carcinogenic air pollutant 3-nitrobenzanthrone (3-NBA). 3-ABA was investigated for its ability to induce cytochrome P450 1A1 (CYP1A1) and NAD(P)H:quinone oxidoreductase (NQO1) in kidney and lung of rats, and for the influence of such induction on DNA adduct formation by 3-ABA and 3-NBA. NQO1 is the enzyme that reduces 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize 3-ABA to the same intermediate. When activated by cytosolic and and/or microsomal fractions isolated from rat lung, the target organ for 3-NBA carcinogenicity, and kidney, both compounds generated the same DNA-adduct pattern, consisting of five adducts. When pulmonary cytosols isolated from rats that had been treated i.p. with 40 mg/kg bw of 3-ABA were incubated with 3-NBA, DNA adduct formation was up to 1.7-fold higher than in incubations with cytosols from control animals. This increase corresponded to an increase in protein level and enzymatic activity of NQO1. In contrast, no induction of NQO1 expression by 3-ABA treatment was found in the kidney. Incubations of 3-ABA with renal and pulmonary microsomes of 3-ABA-treated rats led to an increase of up to a 4.5-fold in DNA-adduct formation relative to controls. The stimulation of DNA-adduct formation correlated with a higher protein expression and activity of CYP1A1 induced by 3-ABA. These results show that by inducing lung and kidney CYP1A1 and NQO1, 3-ABA increases its own enzymatic activation as well as that of the environmental pollutant, 3-NBA, thereby enhancing the genotoxic and carcinogenic potential of both compounds.en
dc.description.sponsorshipThis work was supported in part by the Grant Agency of the Czech Republic, grant 203/06/0329, the Ministry of Education of the Czech Republic, grants MSM0021620808 and 1M0505, the German Cancer Research Center and by Cancer Research UK. V.M. Arlt and D.H. Phillips are partners of ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943).en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2D-4W6XW3R-1&_user=1843694&_coverDate=05%2F31%2F2009&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=dd9e0a0a588c5ae02662c8617c839eb8&searchtype=aen
dc.subjectBenz(a)Anthracenesen
dc.subjectBiotransformationen
dc.subjectCytochrome P-450 CYP1A1en
dc.subjectCarcinogensen
dc.subjectDNA Adductsen
dc.subjectKidneyen
dc.subjectLungen
dc.subject.meshAnimals-
dc.subject.meshBenz(a)Anthracenes-
dc.subject.meshBiotransformation-
dc.subject.meshCarcinogens, Environmental-
dc.subject.meshCytochrome P-450 CYP1A1-
dc.subject.meshDNA Adducts-
dc.subject.meshHumans-
dc.subject.meshKidney-
dc.subject.meshLung-
dc.subject.meshMale-
dc.subject.meshMicrosomes-
dc.subject.meshNAD(P)H Dehydrogenase (Quinone)-
dc.subject.meshRats-
dc.subject.meshRats, Wistar-
dc.title3-aminobenzanthrone, a human metabolite of the carcinogenic environmental pollutant 3-nitrobenzanthrone, induces biotransformation enzymes in rat kidney and lung.en
dc.typeArticleen
dc.identifier.journalMutation Researchen

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