Dibenzo[a,I]pyrene: The Most Potent Carcinogenic Aromatic Hydrocarbon

Abstract

Dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogen among dibenzo[a]pyrenes. DB[a,l]P is more tumorigenic than 7,12−dimethylbenz[a]anthracene, DB[a,l]P 11,12−dihydrodiol, and 100–200 times more tumorigenic than benzo[a]pyrene. DB[a,l]P is also extremely toxic. Dose-response studies were conducted in the skin of female SENCAR mice by initiation-promotion to compare the tumorigenicity of DB[a,l]P to that of (±)−trans−DB[a,l]P−11, 12−dihydrodiol, (±)−anti−DB[a,l]P diol epoxide (anti−DB[a,l]PDE) and (±)−syn−DB[a,l]PDE. Mice were initiated with 12, 4 or 1.33 nmol of compound and promoted with tetradecanoyl phorbol acetate. DB[a,l]P at 12, 4 or 1.33 nmol induced 9.3, 7.1 or 5.2 tumors per mouse (t/m), respectively. DB[a,l]P−11,12−dihydrodiol induced 4.6, 4.3 or 2.8 t/m. Anti−DB[a,l]PDE resulted in 2.0, 0.7 or 0.7 t/m vs 1.8, 1.5 or 1.8 with syn−DB[a,l]PDE. The experiment confirms that DB[a,l]P is more potent than DB[a,l]P−11,12−dihydrodiol and shows that the two diol epoxides are less tumorigenic than their 11, 12−dihydrodiol precursor. At low doses syn−DB[a,l]PDE is a stronger tumor initiator than its congener anti−DB[a,l]PDE.