Polycyclic aromatic hydrocarbons as skin carcinogens: comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse.

2.50
Hdl Handle:
http://hdl.handle.net/10146/269635
Title:
Polycyclic aromatic hydrocarbons as skin carcinogens: comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse.
Authors:
Siddens, Lisbeth K.; Larkin, Andrew; Krueger, Sharon K.; Bradfield, Christopher A.; Waters, Katrina M.; Tilton, Susan C.; Pereira, Cliff B.; Löhr, Christiane V.; Arlt, Volker M.; Phillips, David H.; Williams, David E.; Baird, William M.
Abstract:
The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by ³²P post-labeling, did not correlate with tumor incidence. PAH-dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p<0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs).
Citation:
Toxicol. Appl. Pharmacol. 2012, 264 (3):377-386
Journal:
Toxicology and Applied Pharmacology
Issue Date:
1-Nov-2012
URI:
http://hdl.handle.net/10146/269635
DOI:
10.1016/j.taap.2012.08.014
PubMed ID:
22935520
Additional Links:
http://www.sciencedirect.com/science/article/pii/S0041008X12003560
Type:
Article
Language:
en
ISSN:
1096-0333
Sponsors:
This work was supported by the National Institute of Environmental Health (grants P42ES016465 and P42ES016465-S1). Work at King's College London is supported by Cancer Research UK. Volker M. Arlt and David H. Phillips are members of ECNIS2 (Environmental Cancer Risk, Nutrition and Individual Susceptibility 2), a European Union network of excellence.
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Full metadata record

DC FieldValue Language
dc.contributor.authorSiddens, Lisbeth K.en_GB
dc.contributor.authorLarkin, Andrewen_GB
dc.contributor.authorKrueger, Sharon K.en_GB
dc.contributor.authorBradfield, Christopher A.en_GB
dc.contributor.authorWaters, Katrina M.en_GB
dc.contributor.authorTilton, Susan C.en_GB
dc.contributor.authorPereira, Cliff B.en_GB
dc.contributor.authorLöhr, Christiane V.en_GB
dc.contributor.authorArlt, Volker M.en_GB
dc.contributor.authorPhillips, David H.en_GB
dc.contributor.authorWilliams, David E.en_GB
dc.contributor.authorBaird, William M.en_GB
dc.date.accessioned2013-02-15T12:54:24Z-
dc.date.available2013-02-15T12:54:24Z-
dc.date.issued2012-11-01-
dc.identifier.citationToxicol. Appl. Pharmacol. 2012, 264 (3):377-386en_GB
dc.identifier.issn1096-0333-
dc.identifier.pmid22935520-
dc.identifier.doi10.1016/j.taap.2012.08.014-
dc.identifier.urihttp://hdl.handle.net/10146/269635-
dc.description.abstractThe polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by ³²P post-labeling, did not correlate with tumor incidence. PAH-dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p<0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs).en_GB
dc.description.sponsorshipThis work was supported by the National Institute of Environmental Health (grants P42ES016465 and P42ES016465-S1). Work at King's College London is supported by Cancer Research UK. Volker M. Arlt and David H. Phillips are members of ECNIS2 (Environmental Cancer Risk, Nutrition and Individual Susceptibility 2), a European Union network of excellence.en_GB
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0041008X12003560en_GB
dc.rightsArchived with thanks to Toxicology and applied pharmacologyen_GB
dc.subjectPolycyclic aromatic hydrocarbonen_GB
dc.subjectBenzo(a)pyreneen_GB
dc.subjectDibenzo[def,p]chryseneen_GB
dc.subjectCarcinogensen_GB
dc.subjectToxicityen_GB
dc.subjectAnimalsen_GB
dc.subjectSkin Neoplasmsen_GB
dc.subjectGene expressionen_GB
dc.subjectDNA adductsen_GB
dc.subject.meshAnimals-
dc.subject.meshBenzo(a)pyrene-
dc.subject.meshBenzopyrenes-
dc.subject.meshCarcinogens, Environmental-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshMice-
dc.subject.meshMice, Inbred Strains-
dc.subject.meshMolecular Structure-
dc.subject.meshPrincipal Component Analysis-
dc.subject.meshProtein Array Analysis-
dc.subject.meshSkin Neoplasms-
dc.subject.meshTranscriptome-
dc.titlePolycyclic aromatic hydrocarbons as skin carcinogens: comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse.en
dc.typeArticleen
dc.identifier.journalToxicology and Applied Pharmacologyen_GB

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