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Characterization of a new biotransformation pathway of bisphenol A and quantitation of DNA lesions in HL-60 and MCF-7 cells

Abstract

Bisphenol A (BPA) is largely used for plastic production and widely distributed in the environment, which favors chronic human exposure to this xenobiotic since the intrauterine stage. There is great concern about increased risk of development of different types of cancer by BPA exposure, being that four modes of BPA action are considered to contribute to this increase: endocrine estrogenic disruption, induction of tumor progression, genotoxicity, and development reprogramming with increased susceptibility to other carcinogenic events. In vitro and in vivo studies have revealed these modes of action, but studies are currently necessary to understand the underlying mechanisms to the observed effects.As BPA induces damage to the bone marrow and cancer to the hematopoietic system of rodents, one objective here is to investigate DNA alterations in HL-60 cells due to BPA biotransformation by myeloperoxidase (MPO). Such biotransformation pathway has not been investigated yet. The influence of BPA biotransformation by cytochrome P450 and of its binding to estrogen receptors for induction of DNA alterations will be also evaluated in MCF-7 cells. For this purpose, a set of DNA adducts induced by BPA will be obtained to serve as standards for quantitation in DNA of the exposed cells. Lesions due to oxidative damage, resulting from ROS or a,b-unsaturated aldehyde binding to DNA, will be also quantitated in cell DNA, as well as the global DNA methylation. Such approach will allow to define the importance of some DNA adducts as markers for biological damage monitoring induced by BPA in vivo, beyond the knowledge of the underlying mechanisms for DNA lesion induction. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE OLIVEIRA, TIAGO FRANCO; FELCAO DE OLIVEIRA, ANTONIO ANAX; LEMOS, MIRIAM; VERAS, MARIANA; NASCIMENTO SALDIVA, PAULO HILARIO; GENNARI DE MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; DE MELO LOUREIRO, ANA PAULA. Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 147 MAY 2019. Web of Science Citations: 0.
FALCAO DE OLIVEIRA, ANTONIO ANAX; DE OLIVEIRA, TIAGO FRANCO; DIAS, MICHELLE FRANCINI; GENNARI MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; VERAS, MARIANA; LEMOS, MIRIAM; MARCOURAKIS, TANIA; NASCIMENTO SALDIVA, PAULO HILARIO; MELO LOUREIRO, ANA PAULA. Genotoxic and epigenotoxic effects in mice exposed to concentrated ambient fine particulate matter (PM2.5) from SAo Paulo city, Brazil. PARTICLE AND FIBRE TOXICOLOGY, v. 15, OCT 19 2018. Web of Science Citations: 9.
DE OLIVEIRA, TIAGO FRANCO; MEDEIROS DA SILVA, AMANDA LUCILA; DE MOURA, RAFAELA ALVES; BAGATTINI, RAQUEL; FALCAO DE OLIVEIRA, ANTONIO ANAX; GENNARI DE MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; DE ARRUDA CAMPOS, IVAN PERSIO; BARRETTO, FABIANO PRADO; HENRIQUES BECHARA, ETELVINO JOSE; DE MELO LOUREIRO, ANA PAULA. Luminescent threat: toxicity of light stick attractors used in pelagic fishery. SCIENTIFIC REPORTS, v. 4, JUN 19 2014. Web of Science Citations: 6.

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