Investigação de lesões em DNA induzidas pelo hidrocarboneto policíclico aromático antantreno / Investigation of DNA damage induced by polycyclic aromatic hydrocarbon anthanthrene.

AUTOR(ES)

Igo Dutra

DATA DE PUBLICAÇÃO

2007

RESUMO

Anthanthrene is a polycyclic aromatic hydrocarbon (PAH) widely spread in the environment and does not have the bay or fjord regions, which in general provide high reactivity to these compounds after oxidation. However, its mutagenic activity to bacteria after metabolic activation is comparable to that of benzopyrene (BP) and, based on the sensitivity of the S. typhimurium strains used, anthanthrene metabolites cause base pair substitutions, DNA strand exchanges, and possibly DNA oxidative damage. Some of the metabolites that are genotoxic to bacteria have been recently identified, but a better investigation on how these and other possible metabolites react with biomolecules, identifying the generated adducts, can contribute to clarify the ways involved in its genotoxicity. In the present work we investigated the reaction of anthanthrene (chemically oxidized or oxidized by the HRP/H2O2 system) with dG and DNA in vitro. The formation of possible adducts was observed in the analyses by HPLC/ESI/MS, HPLC/UV/Fluorescence and spectrofluorimetry. Human hepatocelular carcinoma cell line (HepG2) and normal human liver hepatocytes (THLE-2) were incubated with anthanthrene and its oxidation products (quinones and acetyladet hidroquinones). Dose dependent cytotoxity was observed under different culture conditions. As the relative survival of the THLE-2 cells grown on a film of collagen in PFMR-4 medium was very close to the relative survival of the HepG2 cells grown in DME medium, without the collagen film, we used the HepG2 cells for analysis of oxidative damage. Anthanthrene oxidation products (quinones and acetylated hidroquinones) induced 8-oxodGuo formation in the cellular DNA. Data obtained indicate that two ways may be involved in the genotoxicity of anthanthrene observed in the S. typhimurium studies conducted by Platt et al. (2002): DNA oxidative damage and adducts formation.

ASSUNTO(S)

lesões oxidative stress dna adducts. lesions dna estresse oxidativo adutos.

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