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The roles of diol epoxide and o-quinone pathways in mouse lung tumorigenesis induced by benzo(a)pyrene: relevance to human lung carcinogenesis
Citation:
NESNOW, S. The roles of diol epoxide and o-quinone pathways in mouse lung tumorigenesis induced by benzo(a)pyrene: relevance to human lung carcinogenesis. Presented at International Symposium Polycyclic Armaotic Compounds(ISPAC), New Orleans, LA, September 20 - 24, 2009.
Impact/Purpose:
Phenobarbital is used in human relevancy determinations as the mouse liver carcinogen that is not a human carcinogen, and thus its rodent tumor effects are not relevant to humans. This paper provides detailed aproaches and methods using transcriptional analyses that assist in the comparison of chemical carcinogens with PB to identify commonalities and differences.
Description:
There is sufficient epidemiological evidence supported by experimental data that some PAH-containing complex environmental mixtures pose risks to human health by increasing lung cancer incidence. The International Agency for Research on Cancer has determined that human respiratory cancer has been strongly associated with occupational exposures during: coal gasification, coke production, coal-tar distillation, paving and roofing with coal-tar pitch, aluminum production, and with cigarette smoking. Moreover, benzo[a]pyrene (B[a]P), a common constituent in each of these exposures has also been classified as carcinogenic to humans. This presentation will focus on, and summarize, the major findings on the roles of two major B[a]P metabolic activation pathways in the lung tumorigenesis process; the diol epoxide pathway, and the o-quinone pathway. Both pathways initially involve the metabolism of B[a]P to B[aJP-7,8-diol however, their pathways diverge with regard to the types of metabolites, DNA damage, and mutations that are formed and that can lead to cancer induction. Data from experimental systems (literature sources and current experimental data) and from published molecular epidemiological studies will be presented. The associations between B[a]P-induced DNA modifications and alterations in tumor oncogenes and tumor suppressor genes in rodents and in human populations will be a focus of this presentation. The scientific bases for the relative contributions of each mechanism in the process of B[a]P-associated rodent and human lung tumorigenesis will be discussed. This abstract does not reflect EPA Policy