Carcinogenicity of Polycyclic Aromatic Hydrocarbons

Abstract

publicado na web em 01/06/2016 CARCINOGENICITY OF POLYCYCLIC AROMATIC HYDROCARBONS. The assessment of the carcinogenic potential of polycyclic aromatic hydrocarbons (PAH) is obtained by a principal component analysis (PCA) and quantitative structure-activity relationship (QSAR) using hydrophobic (LogP), stereo and electronic parameters (electron affinity, dipole moment and HOMO-LUMO gap) calculated from the AM1 method. The PAH-DNA interaction model is based on the unsynchronized resonating valence bond theory (RVB) developed by L. Pauling. The QSAR study reproduces the experimental values of LD50 in rats with 95% confidence. The PCA analysis classify all the selected compounds as potential carcinogens, an important result since many of these PAH are not classified as carcinogens, indicating the need for an urgent revision of its classification.Keyword: polycyclic aromatic hydrocarbon (PAH); quantitative structure-activity relationship (QSAR); LD50; principal component analysis (PCA); AM1 calculations. INTRODUÇÃOFormados na queima do material orgânico através da combustão incompleta ou pirólise de materiais, os hidrocarbonetos policíclicos aromáticos (HPA) são uma classe de compostos exaustivamente estudados, devido principalmente ao seu potencial carcinogênico e mutagênico.1,2 A variedade de fontes de HPA, incluindo a extensa exaustão de motores a diesel ou à gasolina, queima de carvão e churrascos, resulta em misturas muito complexas, contendo grande variedade de hidrocarbonetos em diferentes níveis de concentração. 2,3Os HPA e seus derivados estão associados à incidência de câncer, sendo que alguns já estão incluídos nas Grupos I e II da International Agency for Research on Cancer (IARC). 4 Entretanto a maioria dos HPA aqui estudados se classificam no Grupo 3 da IARC, ou seja, eles não são classificados quanto à sua carcinogenicidade. Neste trabalho, desenvolvemos um modelo que permite caracterizar o potencial carcinogênico destas espécies químicas utilizando parâmentros eletrônicos obtidos por cálculos de orbitais moleculares combinados a uma análise estatística multivariada de Componentes Principais (ACP) e à Relação Quantitativa da Estrutura-Atividade (QSAR). Trata-se de uma metodologia muito mais rápida e de baixo custo do que a verificação experimental, que apresenta um elevado grau de confiabilidade para a identificação de carcinógenos, podendo assim ser bastante útil na construção de uma política de precaução. Por exemplo, nossos resultados motram que aqueles HPA que estão na lista 3 do IARC precisam ser urgentemente reavaliados. Ativação metabólica dos HPAOs HPA não interagem diretamente com o material genético, eles entram no organismo através da pele, boca e outros pontos de entrada, mas depois sofrem ativações enzimáticas através do citocromo P450, formando metabólitos com elevada natureza eletrofílica denominados carcinógenos efetivos. Os novos compostos podem agora interagir com o DNA e RNA e possibilitar o surgimento de tumores.

Polycyclic Aromatic Hydrocarbons in Foods: Biological Effects, Legislation, Occurrence, Analytical Methods, and Strategies to Reduce Their Formation

“…The most appropriate sorbents are silica, C18, florisil, or a mixture of any two of these. This technique has been widely used owing to its sensitivity and speed [21,25]. Recently, methodologies using fewer and less toxic solvents have been adopted.…”

“…These metabolites can bind to proteins and DNA, forming DNA adducts that lead to biochemical disruptions and cellular damage, consequently causing carcinogenic, mutagenic, immunosuppressive, and teratogenic damage. These genetic mutations are associated with the development of fetal malformations and tumors [21][22][23][24]. In addition, considering that PAHs commonly exist as a complex mixture of different structures, they can exhibit synergistic effects, possibly increasing their toxicity [2].…”

Polycyclic aromatic hydrocarbons and development of respiratory and cardiovascular diseases in workers

“…Cumulative and medium exposures to PAH are positively associated with mortality from COPD (28) . Studies have indicated that PAH do not act directly with the genetic material after being absorbed by the body, they are instead activated through the metabolic process, in which there is the formation of watersoluble compounds to facilitate the excretion process and, in this way, these metabolites interact with the genetic material of cells giving rise to the process of tumoration or mutation (2)(3) .…”

“…Some diseases may be associated with work involving exposure to polycyclic aromatic hydrocarbons (PAH) present in various types of smoke. Mixtures containing PAH may cause several forms of harm to the human body, such as mutagenicity and predisposition to develop cancers (2) .…”

Using an Electrochemical MIP Sensor for Selective Determination of 1‐Naphthol in Oilfield Produced Water

“…Studies published in the literature have investigated the toxicity of naphthalene, and the results show that the harmful effects caused by this compound in mammalian organisms are mainly due to its metabolic products; these products, which include 1-naphthol (1-Nph) and naphthoquinones, have been found to exhibit cytotoxicity [7][8][9]. In addition, 1-Nph is one of the main compounds derived from the degradation of naphthalene under UV-Vis in aqueous medium with dissolved oxygen [8]; this compound is quite prevalent in the marine environment.…”