| First Author | Siddens LK | Year | 2012 |
| Journal | Toxicol Appl Pharmacol | Volume | 264 |
| Issue | 3 | Pages | 377-86 |
| PubMed ID | 22935520 | Mgi Jnum | J:188918 |
| Mgi Id | MGI:5442626 | Doi | 10.1016/j.taap.2012.08.014 |
| Citation | Siddens LK, et al. (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):377-86 |
| abstractText | 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 20weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12h post initiation and analyzed by (32)P post-labeling, did not correlate with tumor incidence. PAH-dependent alteration in transcriptome of skin 12h 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). |
