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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

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 (4 nmol) 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 {sup 32}P 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 DBCmore » 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). -- Highlights: ► Dibenzo[def,p]chrysene (DBC), 3 PAH mixtures, benzo[a]pyrene (BaP) were compared. ► DBC and 2 PAH mixtures were more potent than Relative Potency Factor estimates. ► Transcriptome profiles 12 hours post initiation were analyzed by microarray. ► Principle components analysis of alterations revealed treatment-based clustering. ► DBC gave a unique pattern of gene alterations compared to BaP and PAH mixtures.« less

Authors:
;  [1];  [2];  [3];  [2];  [4]; ;  [3];  [2];  [3];  [2];  [2];  [5];  [2]; ;  [6];  [1];  [2];  [2];  [2] more »; « less
  1. Department of Environmental and Molecular Toxicology, Oregon State University (United States)
  2. (United States)
  3. Superfund Research Center, Oregon State University (United States)
  4. McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706 (United States)
  5. Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States)
  6. Analytical and Environmental Sciences Division, MRC-HPA Centre for Environment and Health, King's College London, London SE1 9NH (United Kingdom)
Publication Date:
OSTI Identifier:
22215958
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 264; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETATES; BENZOQUINONES; CALIBRATION STANDARDS; CARCINOGENS; CARCINOMAS; CHRYSENE; COAL TAR; CONDENSATES; DNA ADDUCTS; EPIDERMIS; EPOXIDES; GLUTATHIONE; LIGASES; MICE; NAD; OXYGEN; OXYGEN 12; POLYCYCLIC AROMATIC HYDROCARBONS; PYRENE; TOBACCO SMOKES; TOLUENE

Citation Formats

Siddens, Lisbeth K., Larkin, Andrew, Superfund Research Center, Oregon State University, Krueger, Sharon K., The Linus Pauling Institute, Oregon State University, Bradfield, Christopher A., Waters, Katrina M., Tilton, Susan C., Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352, Pereira, Cliff B., Deptartment of Statistics, Oregon State University, Corvallis, OR 97331, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, Löhr, Christiane V., College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, Arlt, Volker M., Phillips, David H., Williams, David E., E-mail: david.williams@oregonstate.edu, Superfund Research Center, Oregon State University, The Linus Pauling Institute, Oregon State University, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, and and others. Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.08.014.
Siddens, Lisbeth K., Larkin, Andrew, Superfund Research Center, Oregon State University, Krueger, Sharon K., The Linus Pauling Institute, Oregon State University, Bradfield, Christopher A., Waters, Katrina M., Tilton, Susan C., Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352, Pereira, Cliff B., Deptartment of Statistics, Oregon State University, Corvallis, OR 97331, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, Löhr, Christiane V., College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, Arlt, Volker M., Phillips, David H., Williams, David E., E-mail: david.williams@oregonstate.edu, Superfund Research Center, Oregon State University, The Linus Pauling Institute, Oregon State University, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, & and others. Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse. United States. doi:10.1016/J.TAAP.2012.08.014.
Siddens, Lisbeth K., Larkin, Andrew, Superfund Research Center, Oregon State University, Krueger, Sharon K., The Linus Pauling Institute, Oregon State University, Bradfield, Christopher A., Waters, Katrina M., Tilton, Susan C., Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352, Pereira, Cliff B., Deptartment of Statistics, Oregon State University, Corvallis, OR 97331, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, Löhr, Christiane V., College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, Arlt, Volker M., Phillips, David H., Williams, David E., E-mail: david.williams@oregonstate.edu, Superfund Research Center, Oregon State University, The Linus Pauling Institute, Oregon State University, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, and and others. Thu . "Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse". United States. doi:10.1016/J.TAAP.2012.08.014.
@article{osti_22215958,
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},
author = {Siddens, Lisbeth K. and Larkin, Andrew and Superfund Research Center, Oregon State University and Krueger, Sharon K. and The Linus Pauling Institute, Oregon State University and Bradfield, Christopher A. and Waters, Katrina M. and Tilton, Susan C. and Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 and Pereira, Cliff B. and Deptartment of Statistics, Oregon State University, Corvallis, OR 97331 and Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 and Löhr, Christiane V. and College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 and Arlt, Volker M. and Phillips, David H. and Williams, David E., E-mail: david.williams@oregonstate.edu and Superfund Research Center, Oregon State University and The Linus Pauling Institute, Oregon State University and Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 and and others},
abstractNote = {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 (4 nmol) 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 {sup 32}P 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). -- Highlights: ► Dibenzo[def,p]chrysene (DBC), 3 PAH mixtures, benzo[a]pyrene (BaP) were compared. ► DBC and 2 PAH mixtures were more potent than Relative Potency Factor estimates. ► Transcriptome profiles 12 hours post initiation were analyzed by microarray. ► Principle components analysis of alterations revealed treatment-based clustering. ► DBC gave a unique pattern of gene alterations compared to BaP and PAH mixtures.},
doi = {10.1016/J.TAAP.2012.08.014},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 264,
place = {United States},
year = {2012},
month = {11}
}