Genotoxic and epigenotoxic effects in mice exposed to concentrated ambient fine particulate matter (PM2.5) from SAo Paulo city, Brazil

Author(s)

Falcao de Oliveira, Antonio Anax ^[1] ; de Oliveira, Tiago Franco ^{[1, 2]} ; Dias, Michelle Francini ^[1] ; Gennari Medeiros, Marisa Helena ^[3] ; Di Mascio, Paolo ^[3] ; Veras, Mariana ^[4] ; Lemos, Miriam ^[4] ; Marcourakis, Tania ^[1] ; Nascimento Saldiva, Paulo Hilario ^{[4, 5]} ; Melo Loureiro, Ana Paula ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Ave Prof Lineu Prestes 580, Bloco 13 B, BR-05508000 Sao Paulo - Brazil

^[2] Univ Fed Ciencias Saude Porto Alegre, Dept Farmacociencias, Rua Sarmento Leite 245, BR-90050170 Porto Alegre, RS - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, Ave Prof Lineu Prestes 748, BR-05508000 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Hosp Clin, Lab Poluicao Atmosfer Expt LIM05, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Estudos Avancados, R Anfiteatro 513, BR-05508060 Sao Paulo - Brazil

• Document type: Journal article
• Source: PARTICLE AND FIBRE TOXICOLOGY; v. 15, OCT 19 2018.
• Web of Science Citations: 9

Abstract

BackgroundThe Metropolitan Area of SAo Paulo has a unique composition of atmospheric pollutants, and positive correlations between exposure and the risk of diseases and mortality have been observed. Here we assessed the effects of ambient fine particulate matter (PM2.5) on genotoxic and global DNA methylation and hydroxymethylation changes, as well as the activities of antioxidant enzymes, in tissues of AJ mice exposed whole body to ambient air enriched in PM2.5, which was concentrated in a chamber near an avenue of intense traffic in SAo Paulo City, Brazil.ResultsMice exposed to concentrated ambient PM2.5 (1h daily, 3months) were compared to in situ ambient air exposed mice as the study control. The concentrated PM2.5 exposed group presented increased levels of the oxidized nucleoside 8-oxo-7,8-dihydro-2-deoxyguanosine in lung and kidney DNA and increased levels of the etheno adducts 1,N-6-etheno-2-deoxyadenosine and 1,N-2-etheno-2-deoxyguanosine in kidney and liver DNA, respectively. Apart from the genotoxic effects, the exposure to PM2.5 led to decreased levels of the epigenetic mark 5-hydroxymethylcytosine (5-hmC) in lung and liver DNA. Changes in lung, liver, and erythrocyte antioxidant enzyme activities were also observed. Decreased glutathione reductase and increased superoxide dismutase (SOD) activities were observed in the lungs, while the liver presented increased glutathione S-transferase and decreased SOD activities. An increase in SOD activity was also observed in erythrocytes. These changes are consistent with the induction of local and systemic oxidative stress.ConclusionsMice exposed daily to PM2.5 at a concentration that mimics 24-h exposure to the mean concentration found in ambient air presented, after 3months, increased levels of DNA lesions related to the occurrence of oxidative stress in the lungs, liver, and kidney, in parallel to decreased global levels of 5-hmC in lung and liver DNA. Genetic and epigenetic alterations induced by pollutants may affect the genes committed to cell cycle control, apoptosis, and cell differentiation, increasing the chance of cancer development, which merits further investigation. (AU)

• FAPESP's process: 12/08617-4 - Variables on glycemic control and pathogenesis of diabetic nephropathy: research on the phenomenon of metabolic memory
• Grantee: Antonio Anáx Falcão de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 12/08616-8 - Characterization of a new biotransformation pathway of bisphenol A and quantitation of DNA lesions in HL-60 and MCF-7 cells
• Grantee: Ana Paula de Melo Loureiro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/09891-0 - Genotoxic and epigenetic changes in DNA of mice exposed to particulate matter (PM 2,5)
• Grantee: Antonio Anáx Falcão de Oliveira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 12/22190-3 - The role of metabolic memory in the development of diabetic nephropathy
• Grantee: Ana Paula de Melo Loureiro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/21636-8 - Transformation of human bronchial epithelial cells by benzo[a]pyrene: metabolic redox processes and DNA methylation / demethylation
• Grantee: Tiago Franco de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC