Bladder cancer associated with elevated heavy metals: Investigation of probable carcinogenic pathways through mitochondrial dysfunction, oxidative stress and mitogen-activated protein kinase.

Autor: Ali-El-Dein B; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Electronic address: balieldein@yahoo.com., Abdelgawad M; Toshka Urology and Endoscopy center, Mansoura, Egypt., Tarek M; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Abdel-Rahim M; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Elkady ME; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Saleh HH; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Zakaria MM; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Tarabay HH; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Laymon M; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Mosbah A; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Stenzl A; Department of Urology, University of Tuebingen Medical School, Tuebingen, Germany.
Jazyk: angličtina
Zdroj: Urologic oncology [Urol Oncol] 2024 Oct 07. Date of Electronic Publication: 2024 Oct 07.
DOI: 10.1016/j.urolonc.2024.09.009
Abstrakt: Objective: Carcinogenic mechanisms of heavy metals/ trace elements (HMTE) in bladder cancer (BC) are exactly unknown. Mitochondrial dysfunction (MD), oxidative stress (OS), and mitogen-activated protein kinases (MAPK) are probable carcinogenic mechanisms. The purpose is to investigate probable carcinogenic pathways of HMTE in BC using six MD genes, seven OS markers, and p38-MAPK.
Methods: Study included 125 BC/radical cystectomy (RC) patients between October 2020 and October 2022, and 72 controls. Exclusion criteria included previous neoplasm, chemo- or radiotherapy. Two samples (cancer/noncancer) were taken from RC specimens. Tissues/plasma/urine cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), strontium (Sr), aluminium (Al), zinc (Zn), boron (B) were measured by ICP-OES. Tissue MD genes (mt-CO3, mt-CYB, mt-ATP 6, mt-ATP8, mt-CO1, mt-ND1), and serum OS markers (8-OHdG, MDA, 3-NT, AGEs, AOPP, ROS, SOD2), p38-MAPK were assessed by RT-PCR, and ELISA, respectively.
Results: BC and adjacent tissue showed higher (Al, Co, Pb, Ni, Zn, Cd,Sr), lower B concentrations, compared to controls. High tissue concentrations (Cd, Co, Pb, Ni, Sr) were associated with higher MD genes, OS, MAPK and lower SOD2 levels. The same differences were greater in 41 patients with concomitant elevation of two or more HMTE. Noninclusion of BC-related oncogenes (e.g. RAS) is a limitation.
Conclusions: Evidence suggests that high BC tissue (Cd, Co, Pb, Ni, Si) concentrations are associated with over-expressed MD genes, OS, p38-MAPK and low SOD2. These findings provide important understanding keys of probable carcinogenic pathways in BC associated with HMTE. So, efforts should be performed to minimize and counteract exposure to toxic HMTE.
Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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