Banca de DEFESA: FRANCISCO CARLOS DA SILVA JUNIOR

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : FRANCISCO CARLOS DA SILVA JUNIOR
DATE: 07/02/2023
TIME: 14:00
LOCAL: Videoconferencia
TITLE:

A Look beyond the priority: A comprehensive investigation of the toxicity of retene

KEY WORDS:

PAH, Retene; Non-priority; Toxic endpoints; Risk assessment.

PAGES: 285
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Particulate matter (PM) is considered one of the greatest threats to human health worldwide, there is still significant uncertainty and knowledge gaps with regard to many of the chemicals responsible for these effects such as PAHs. Polycyclic Aromatic Hydrocarbons (PAHs) are a wide class of chemical compounds with significant mutagenic and carcinogenic potentials, thereby harming human well-being. The United States – Environmental Protection Agency (US-EPA) includes 16 priority PAHs in risk assessment or routine environmental analyses. Retene (1-methyl-7-isopropylphenanthrene; RET), a non-priority PAH, is one of the most widely produced PAHs following forest fires. At present, the toxic endpoints of RET remain unknown, especially in human health. Therefore, divided into five chapters, this work comprehensively investigated the toxic endpoints of RET. In the first chapter, through a systematic review and meta-analysis, it was demonstrated the presence of an association between exposure to PM and genetic instability in different human population, which this early damage may lead to susceptibility to complex diseases, including lung cancer. The second chapter demonstrated that much of the knowledge on the PAHs is restricted to the priority ones; however, there are other non-priority PAHs in the environment, whose mutagenic and carcinogenic potentials are underestimated in risk assessments and routine environmental analysis, especially RET. In the third chapter, using human lung cells (A549), the results revealed that RET can significantly decrease cell viability, increase oxidative stress, mitochondrial membrane potential, and mitochondrial contents, leading to an increased reactive oxygen species (ROS) production. Besides, RET led to a significant increase in chromosomal mutations such as micronuclei (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) frequency but not mutagenicity in Salmonella strains, as well as cell death, mainly due to necrosis. The fourth chapter showed, using in-silico analysis of differentially expressed genes (DEGs), interaction networks, and transcriptional profiles in A549 cells, that RET induced variations in several genes related to metabolism, transcriptional and translational control, oxidative stress, cell cycle, DNA replication, and repair. Genes involved in these processes may explain the toxic phenotypes demonstrated using the in-silico analyses such as genotoxicity, mutagenicity, and carcinogenicity. In the fifth chapter, using zebrafish (Danio rerio) as an experimental model, RET affected DNA generating micronuclei in erythrocytes and provided new evidence suggesting behavioral alterations due to changes in redox status and the mRNA expression of the neurotransmitter systems in zebrafish brains. Overall, these results reinforce the need to look beyond the priority in toxicological research on PAHs, especially those whose toxic potentials remain underestimated such as RET, highlighting the importance of including this PAH in risk assessments and routine environmental analysis in the future especially due its toxic effects in humans.

COMMITTEE MEMBERS:
Externo à Instituição - FABIANO PERES MENEZES - UFRN
Externa à Instituição - JULIANA DA SILVA - ULBRA
Externa à Instituição - RENATA CANALLE - UFDPar
Presidente - 1199127 - SILVIA REGINA BATISTUZZO DE MEDEIROS
Interna - 1674709 - VIVIANE SOUZA DO AMARAL