Abstract A02: A case for re-examination of the contribution of nitro-PAHs to combustion-product carcinogenesis
| Autor: | Gary Blackburn |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Cancer Prevention Research. 13:A02-A02 |
| ISSN: | 1940-6215 1940-6207 |
| Popis: | One of the most studied compounds in all of cancer research is the environmental carcinogen benzo[a]pyrene (BaP). There is little doubt that BaP and its PAH congeners are the principal carcinogens in products like coal tar pitch, a category 1 IARC carcinogen. However, their concentrations in other complex hydrocarbon mixtures, like uncracked petroleum oils, are too low to account for their overall carcinogenic potency (that is, discounting contributory factors like tumor promotion and cumulative mutagenic insult). Nonetheless, the potent carcinogenicity of BaP and other four- and five-ring PACs has made reducing the release of these compounds into the environment from their principal endogenous source, petroleum, a major goal of health and safety regulation. Similar efforts to minimize the levels of the same PAHs pyrosynthesized and released into the atmosphere by the combustion of carbon fuels, have, however, faced a far greater challenge, given the immensity of that release on a daily basis. Moreover, the regulatory focus on parent, largely unsubstituted, PAHs has led to a de-emphasis on other potential contributors to the carcinogenicity of complex hydrocarbon mixtures, which in the case of the combustion products studied here, include their nitro-PAH derivatives. There are valid reasons for this de-emphasis. But there are also grounds to believe that a re-examination of the nitro-PAH role in combustion product carcinogenesis is warranted. Among them are the demonstration by Rosenkranz et al. (Science 1980;209:1039-43) that one such compound, 1,8-dinitropyrene (DNP), induces over one million mutations per microgram in the Ames Test, and the Iwagawa et al. report (Carcinogenesis 1989;10:1285-90) that its isomer 1,6-DNP, when injected directly into the lungs of rats, exhibited three times the carcinogenic potency of BaP similarly introduced. The present report demonstrates that extracts of soot or ash from a variety of sources, including wood, liquified petroleum gas, and the burnt ends of cigarettes, contain an extremely potent Ames Test mutagen that, when fractionated by HPLC, coelutes with authentic DNP. These results would seem to be inconsistent with the known low activities in lung tissue of the nitroreductase required for DNP’s activation to its ultimate carcinogenic form. But one possible explanation for that apparent discrepancy is that populations of bacteria resident in the lung—many species of which are as nitroreductase-proficient as the Salmonella strains used in Ames testing—may be largely responsible for that activation. Citation Format: Gary Blackburn. A case for re-examination of the contribution of nitro-PAHs to combustion-product carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A02. |
| Databáze: | OpenAIRE |
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