Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene.

Autor: Vacario BGL; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil.; Laboratory of Tumor Biology, State University of West Paraná (UNIOESTE), Francisco Beltrão, Paraná, Brazil., da Silva IM; Laboratory of Mutagenesis and Oncogenetics, State University of Londrina (UEL), Londrina, Paraná, Brazil., Machado MG; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Orrutéa JFG; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Campos AGH; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Matos RO; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Federige ACL; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Koizumi BY; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Leite MB; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Komori IMS; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Dos Santos Jaques H; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Rech D; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Guembarovski RL; Laboratory of Mutagenesis and Oncogenetics, State University of Londrina (UEL), Londrina, Paraná, Brazil., Amarante MK; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil., Serpeloni JM; Laboratory of Mutagenesis and Oncogenetics, State University of Londrina (UEL), Londrina, Paraná, Brazil., Panis C; Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil.; Laboratory of Tumor Biology, State University of West Paraná (UNIOESTE), Francisco Beltrão, Paraná, Brazil.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2024 Nov; Vol. 38 (11), pp. e70013.
DOI: 10.1002/jbt.70013
Abstrakt: Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.
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Databáze: MEDLINE