PNNL

Abstract

The polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), was compared to, dibenzo[def,p]chrysene (DBC) and combinations of 3 environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) utilizing an FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence in less than 20 weeks of 12-O-tetradecanoylphorbol- 13-acetate (TPA) promotion with a multiplicity 4-times greater than BaP (400 nmol) which also exhibited a longer latency to tumor formation. Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b) did not differ from toluene controls and failed to elicit a carcinogenic response, whereas addition of coal tar extract (1 mg, SRM 1597a) produced a tumor response (incidence, multiplicity and type) similar to BaP. Further addition of 2 mg of cigarette smoke condensate did not alter the response seen with diesel plus coal tar. PAH-DNA adducts measured 12 hours post initiation, and analyzed by 32P-post-labeling, were not correlated with tumor incidence. PAH-dependent alteration in the dermal transcriptome was assessed by microarray 12 hours post-treatment. Principal component analysis of the 922 genes significantly (p