Banca de QUALIFICAÇÃO: FRANCISCO CARLOS DA SILVA JUNIOR

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : FRANCISCO CARLOS DA SILVA JUNIOR
DATE: 29/07/2022
TIME: 14:00
LOCAL: Videoconferência
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: 228
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Polycyclic Aromatic Hydrocarbons (PAHs) are a wide class of chemical compounds with significant mutagenic and carcinogenic potentials, thereby harming human well-being. 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 four chapters, the aim objective of this work is comprehensively investigating the toxic endpoints of RET. In the first chapter, through a systematic review, it was 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 second 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, as well as cell death, mainly due to necrosis. The third chapter showed, using an Adverse Outcome Pathway (AOP) framework, as well as through the in-silico analysis of 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 triggered by exposure to this non-priority PAH. In the fourth chapter, using zebrafish (Danio rerio) as an experimental model, RET affected DNA generating micronuclei and provided new evidence suggesting behavioral alterations due to changes in redox status and the mRNA expression of the neurotransmitter systems. Overall, these results reinforce the risk posed by non-priority PAHs especially those whose toxic potentials remain underestimated, highlighting the importance of including RET in risk assessments and routine environmental analysis in the future.

BANKING MEMBERS:
Interna - 1549705 - ADRIANA FERREIRA UCHOA
Externa à Instituição - JULIANA DA SILVA - ULBRA
Presidente - 1674709 - VIVIANE SOUZA DO AMARAL