Percivall Pott (1714-1788), an English surgeon, is generally credited with being the first to suggest that cancer may be induced by exposure to environmental carcinogens – in his case, cancer of the scrotum in London chimney sweeps occupationally exposed to soot. It is perhaps not surprising, therefore, that combustion products became a primary focus of later research into the mechanisms of chemical carcinogenesis. Early on, those studies pointed toward a particular class of compounds as being primarily responsible for cancer induction by such materials, a group of environmentally ubiquitous compounds called polycyclic aromatic hydrocarbons, or PAHs. One such PAH, benzo[a]pyrene (BaP), is perhaps the most studied compound in all of cancer research. While there is little doubt that BaP and its congeners are the primary carcinogens in incomplete combustion products like coal tar, their concentrations in other hydrocarbon mixtures are too low to fully account for their overall carcinogenic potency. It is possible that other factors such as tumor promotion contribute to the additional potency, but it might also be expected that there are significant contributions from nitro-PAH derivatives, in particular the isomers of dinitropyrene (DNP) found in carbon black, diesel exhaust and other combustion products. One such isomer, 1,6-dinitropyrene was shown by Iwagawa et al. to have three-times the carcinogenic potency of BaP when injected directly into the lungs of rats. In order to indirectly test nitroaromatic contribution to combustion product carcinogenicity, extracts of smoke soot, ash and food products exposed to smoke during processing were fractionated by HPLC, and the fractions tested in the Ames Test without metabolic activation. All showed a common peak of extremely potent direct-acting mutagenicity at a retention time similar to that of dinitropyrene. Efforts are currently underway to fully characterize the mutagen by a combination of standard analytical means.
Citation Format: Gary R. Blackburn. Hydrocarbon carcinogenicity reexamined: An extremly potent direct-acting mutagen is common to smoke, soot and ash from a variety of combustion sources, including cigarette tobacco [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3099.