Impact of exposure to plastic waste on functional and oncogenic targets in human prostate cells

• Grant number: 24/22078-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Pedro Henrique da Fonte Portinho
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 22/12304-3 - Repercussions of maternal exposure to nanoplastics and phthalates: maternal aspects and susceptibility to prostatic oncogenesis in rats, AP.R

Abstract

The plastic problem is one of the biggest public health challenges on the planet. Investigations have shown that global plastic production was 400 million tons in 2015, and it is estimated that 12 billion tons of plastic waste will be produced by 2050. When plastics enter the environment, they degrade to form microplastics (MPs) and nanoplastics (NPs) that enter the body through breathing, ingestion of contaminated food and water, and through the skin. Phthalates are additives that give plastic malleability, which do not covalently bind to the polymer, and are therefore easily released into the environment. Phthalates are classified as endocrine disruptors (EDs) and have been detected in different proportions and concentrations in human tissues and fluids. Furthermore, in vivo studies performed in our laboratory demonstrated that a mixture of phthalates, equivalent to that used in this study, deregulated the expression of genes and miRNAs associated with the development and carcinogenic pathways of the prostate. Thus, the main objective of this study was to mimic the conditions of in vivo exposure, with the aim of establishing an in vitro model of chronic exposure to evaluate the pathways related to cell proliferation and death, as well as the migratory potential of cells, the status of the antioxidant system and molecular markers of AR (androgen receptor) and ER (estrogen receptor), using normal prostate epithelial cells exposed to an environmentally relevant mixture of phthalate monoesters and nanoplastics, in proportions similar to those found in humans. The cells will be exposed for 15 and 30 consecutive cycles (passages) to the following treatments: CONTROL (CT): culture medium + DMSO (at the same concentration used in the treatments); TREATMENT 1: culture medium + phthalate mixture; TREATMENT 2: culture medium + nanoparticles; TREATMENT 3: culture medium + mixture + nanoparticles. The MTT test will be performed to determine the doses and concentrations for exposure. For this, the cells will be exposed to 8 increasing concentrations of the mixture of phthalate monoesters and polystyrene microplastics (100 nm), for 24 hours at 37 ºC. In addition, a morphological study of the cells, Wound Healing Assay and analysis of gene expression through the RTq-PCR technique will be performed.