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

Accession Number: GSE39455

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39455

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Expression profiling by array

Organism(s): Mus musculus

Summary: 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 of 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 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).

Publication(s) associated with this dataset:

• Tilton SC, Siddens LK, Krueger SK, Larkin A, Lohr CV, Williams DE, Baird WM, Waters KM. 2015. Mechanism-based classification of PAH mixtures to predict carcinogenic potential. Toxicol Sci 146(1):135-145. doi:10.1093/toxsci/kfv080 PMID:25908611 PMCID:PMC4476464

• Siddens LK, Larkin A, Krueger SK, Bradfield CA, Waters KM, Tilton SC, Pereira CB, Lohr CV, Arlt VM, Phillips DH, Williams DE, Baird WM. 2012. Polycyclic aromatic hydrocarbons as skin carcinogens: comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse. Toxicol Appl Pharmacol 264(3):377-386. doi:10.1016/j.taap.2012.08.014 PMID:22935520 PMCID:PMC3483092

Project(s) associated with this dataset:

• Oregon State University: PAHs in Humans at Environmental Levels: Pharmacokinetics, Metabolism and Susceptible Individuals
• Oregon State University: Data Management and Analysis Core