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dc.contributor.authorSchmeiser, Heinz H.
dc.contributor.authorFurstenberger, Gerhard
dc.contributor.authorTakamura-Enya, Takeji
dc.contributor.authorPhillips, David H.
dc.contributor.authorArlt, Volker M.
dc.date.accessioned2009-10-06T10:42:59Z
dc.date.available2009-10-06T10:42:59Z
dc.date.issued2009-10-18
dc.identifier.citationCancer Lett. 2009, 284 (1):21-29en
dc.identifier.issn1872-7980
dc.identifier.pmid19442433
dc.identifier.doi10.1016/j.canlet.2009.04.003
dc.identifier.urihttp://hdl.handle.net/10146/83594
dc.description.abstract3-Nitrobenzanthrone (3-NBA), a genotoxic mutagen found in diesel exhaust and ambient air pollution and its active metabolite N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) were tested for initiating and complete carcinogenic activity in the NMRI mouse skin carcinogenesis model. Both compounds were found to be inactive as either tumour initiators or complete carcinogens in mouse skin over a dose range of 25-400nmol. Topical application of 3-NBA and N-OH-3-ABA produced DNA adduct patterns in epidermis, detected by (32)P-postlabelling, similar to those found previously in other organs of rats and mice. 24h after a single treatment of 100nmol DNA adduct levels produced by 3-NBA (18+/-4 adducts/10(8) nucleotides) were 6 times lower than those by 7,12-dimethylbenz[a]anthracene (DMBA; 114+/-37 adducts/10(8) nucleotides). In contrast, identical treatment with N-OH-3-ABA resulted in adduct levels in the same range as with DMBA (136+/-25 adducts/10(8) nucleotides), indicating that initial DNA adduct levels do not parallel tumour initiating activity. When compounds were tested for tumour initiating activity by a single treatment followed by twice-weekly applications of TPA, DNA adducts formed by DMBA, but not by 3-NBA or N-OH-3-ABA, were still detectable 40weeks after treatment. When tested for activity as complete carcinogens by twice-weekly topical application, 3-NBA and N-OH-3-ABA produced identical DNA adduct profiles in mouse skin, with adducts still detectable after 40weeks. Only 3-NBA produced detectable adducts in other organs.
dc.description.sponsorshipThe authors acknowledge the excellent technical assistance by Brigitte Steinbauer, German Cancer Research Center, Heidelberg. The study was supported by Cancer Research UK. H.H.S., V.M.A. and D.H.P. are members 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=B6T54-4W8KHSM-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=afdc1aa91187c8d6ba6b70bb3ef28a24en
dc.relation.urlhttp://www.cancerletters.info/article/S0304-3835%2809%2900251-1/abstracten
dc.subject3-Nitrobenzanthroneen
dc.subject7,12-Dimethylbenz[a]anthraceneen
dc.subjectCarcinogenesisen
dc.subjectDNA adducten
dc.subjectDiesel exhausten
dc.subjectAir pollutionen
dc.subject.mesh9,10-Dimethyl-1,2-benzanthracene
dc.subject.meshAir Pollutants
dc.subject.meshAnimals
dc.subject.meshBenz(a)Anthracenes
dc.subject.meshCarcinogens
dc.subject.meshCell Transformation, Neoplastic
dc.subject.meshDNA Adducts
dc.subject.meshDNA Damage
dc.subject.meshEpidermis
dc.subject.meshFemale
dc.subject.meshMice
dc.subject.meshSkin
dc.subject.meshSkin Neoplasms
dc.subject.meshVehicle Emissions
dc.titleThe genotoxic air pollutant 3-nitrobenzanthrone and its reactive metabolite N-hydroxy-3-aminobenzanthrone lack initiating and complete carcinogenic activity in NMRI mouse skin.en
dc.typeArticleen
dc.identifier.journalCancer lettersen
html.description.abstract3-Nitrobenzanthrone (3-NBA), a genotoxic mutagen found in diesel exhaust and ambient air pollution and its active metabolite N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) were tested for initiating and complete carcinogenic activity in the NMRI mouse skin carcinogenesis model. Both compounds were found to be inactive as either tumour initiators or complete carcinogens in mouse skin over a dose range of 25-400nmol. Topical application of 3-NBA and N-OH-3-ABA produced DNA adduct patterns in epidermis, detected by (32)P-postlabelling, similar to those found previously in other organs of rats and mice. 24h after a single treatment of 100nmol DNA adduct levels produced by 3-NBA (18+/-4 adducts/10(8) nucleotides) were 6 times lower than those by 7,12-dimethylbenz[a]anthracene (DMBA; 114+/-37 adducts/10(8) nucleotides). In contrast, identical treatment with N-OH-3-ABA resulted in adduct levels in the same range as with DMBA (136+/-25 adducts/10(8) nucleotides), indicating that initial DNA adduct levels do not parallel tumour initiating activity. When compounds were tested for tumour initiating activity by a single treatment followed by twice-weekly applications of TPA, DNA adducts formed by DMBA, but not by 3-NBA or N-OH-3-ABA, were still detectable 40weeks after treatment. When tested for activity as complete carcinogens by twice-weekly topical application, 3-NBA and N-OH-3-ABA produced identical DNA adduct profiles in mouse skin, with adducts still detectable after 40weeks. Only 3-NBA produced detectable adducts in other organs.


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