High molecular weight polycyclic aromatic hydrocarbon (HMW-PAH) isomers: unveiling distinct toxic effects from cytotoxicity to oxidative stress-induced DNA damage

Author(s)

Ferreira Azevedo, Lara ; de Souza Rocha, Cecilia Cristina ; Souza, Marilia Cristina Oliveira ; Machado, Ana Rita Thomazela ; Devoz, Paula Picoli ; Rocha, Bruno Alves ; Antunes, Lusania Maria Greggi ; Uribe-Romo, Fernando J. ; Campiglia, Andres D. ; Barbosa Jr, Fernando

• Document type: Journal article
• Source: ARCHIVES OF TOXICOLOGY; v. N/A, p. 9-pg., 2024-11-29.

Abstract

Polycyclic aromatic hydrocarbons (PAHs) represent one of the most extensive classes of known carcinogenic and genotoxic compounds widely distributed across the globe. Particularly relevant to ecotoxicological studies is the possible presence of PAHs with molecular weight (MW) 302 Da. Since the toxicity of 302 Da PAHs differs significantly from isomer to isomer, understanding their relative toxicity is essential for assessing their potential risks to human health. This study investigates the toxic effects of micromolar concentrations of four HMW-PAHs isomers of MW = 302 Da, namely dibenzo(b,l)fluoranthene (DB(b,l)F), dibenzo(a,j)fluoranthene (DB(a,j)F), dibenzo(a,l)fluoranthene (DB(a,l)F) and naphtho(1-2j)fluoranthene (N(1-2j)F), upon exposure and metabolic activation in HepG2 cells. Appropriate assays were selected to investigate their potential to disrupt cellular viability and to induce cytotoxicity, apoptosis/necrosis, genotoxicity, and oxidative stress with DNA damage. After 48 h of exposure time, DB(a,l)F was the only isomer to reduce cellular viability in a concentration-dependent manner. In all cases, apoptosis was the main mechanism of HepG2 cell death, which could be induced by the significant DNA damage and an increase in 8-hydroxy-2 '-deoxyguanosine (8-OHdG) adduct level formation. The highest concentrations of DB(a,l)F tested exhibited the greatest potential to induce HepG2 DNA damage and 8-OHdG formation. Altogether, these facts demonstrate that the distinct arrangements of the atoms in HMW-PAHs isomers can impact on their toxic potential and that DB(a,l)F was the most toxic isomer evaluated in this study. These results shed light on the importance to thoroughly characterize MW302 PAHs to substantiate their human and environmental risk assessments. (AU)

• FAPESP's process: 19/07161-6 - Exposure evaluation to pesticides, polycyclic aromatic hydrocarbons, and toxic elements in Brazilian children: establishment of reference values and possible association with oxidative stress biomarkers.
• Grantee: Marília Cristina Oliveira Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/24069-3 - ReSEARCH: Recognizing Signatures of the Exposome to Anticipate the Risks for a Continuous Health
• Grantee: Fernando Barbosa Júnior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/19554-0 - Assessment of mechanisms associated with energy homeostasis disruption after bisphenol A or S exposures through untargeted metabolomics
• Grantee: Lara Ferreira Azevedo
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 22/06443-0 - Bioavailability and bioaccessibility of pesticides and legacy pollutants in food: a public health risk assessment and creation of a risk-benefit tool for Brazilian consumers
• Grantee: Marília Cristina Oliveira Souza
• Support Opportunities: Generation Project Research Grant