MECANISMOS DE ACCIÓN DEL RECEPTOR DE HIDROCARBUROS DE ARILOS EN EL METABOLISMO DEL BENZO[A]PIRENO Y EL DESARROLLO DE TUMORES

Abstract

Benzo[a]pyrene (b[a]p), is a polycyclic aromatic hydrocarbon (PAH) product of incomplete combustion of organic matter. B[a]p is considered as a carcinogen due to the mutagenic and carcinogenic properties of its biotransformation derivatives, such as benzo[a]pyrene diol epoxide (b[a]pDE). B[a]p is metabolized by cytochrome P450 enzymes 1A1 (CYP1A1) and 1B1 (CYP1B1), whose expression is regulated by the aryl hydrocarbon receptor (AhR) signaling pathway. Studies suggest that AhR is involved in the regulation of other cellular processes, in addition to detoxification of xenobiotics, such as development, differentiation, proliferation, immune response, cancer development , and apoptosis, by modulating signaling pathways mediated by protein kinases such as the epidermal growth factor (EGFR). However it is not clear the role of AhR in these processes nor the mechanisms of AhR interaction with other signaling pathways. Cellular changes induced by b[a]p are complex and may be mediated by more than one signaling pathway and by the activation of multiple genes, so it is essential to know which pathways are involved in the metabolism of PAHs for a better understanding of the molecular basis of diseases such as cancer.