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Environ Res. 2019 Nov;178:108700. doi: 10.1016/j.envres.2019.108700. Epub 2019 Aug 28.

Biological and molecular modifications induced by cadmium and arsenic during breast and prostate cancer development.

Author information

1
MEDFUTURE - Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337, Cluj-Napoca, Romania.
2
The Oncology Institute "Prof. Dr. Ion Chiricuta", Republicii 34-36 Street, 400015, Cluj-Napoca, Romania; "Iuliu Hatieganu" University of Medicine and Pharmacy, 8 Victor Babes Street, 400012, Cluj-Napoca, Romania.
3
Cluj School of Public Health, College of Political, Administrative and Communication Sciences, Babes-Bolyai University, 7 Pandurilor Street, Cluj-Napoca, Romania; Environmental Health Center, 58 Busuiocului Street, 400240, Cluj-Napoca, Romania; Faculty of Environmental Science and Engineering, Babes-Bolyai University, 30 Fantanele Street, Cluj- Napoca, Romania.
4
Cantacuzino National Institute of Research and Development for Microbiology, 103 Splaiul Independentei Street, Bucharest, 050096, Romania.
5
"Victor Babes" National Institute of Pathology, 99-101 Splaiul Independentei Street, 050096, Bucharest, Romania.
6
Department of Enzymology, Institute of Biochemistry of the Romanian Academy, 296 Splaiul Independentei Street, Bucharest, 060031, Romania.
7
MEDFUTURE - Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337, Cluj-Napoca, Romania; Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street, 400337, Cluj-Napoca, Romania; Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof. Dr. Ion Chiricuta", Republicii 34-36 Street, Cluj-Napoca, Romania. Electronic address: ioananeagoe29@gmail.com.

Abstract

Breast and prostate cancer are two of the most common malignancies worldwide. Both cancers can develop into hormone -dependent or -independent subtypes and are associated to environmental exposure in the context of an inherited predisposition. As and Cd have been linked to the onset of both cancers, with the exception of As, which lacks a definitive association with breast carcinogenesis. The two elements exert an opposite effect dependent on acute versus chronic exposure. High doses of As or Cd were shown to induce cell death in acute experimental exposure, while chronic exposure triggers cell proliferation and viability, which is no longer limited by telomere shortening and apoptosis. The chronically exposed cells also increase their invasion capacity and tumorigenic potential. At molecular level, malignant transformation is evidenced mainly by up-regulation of BCL-2, MMP-2, MMP-9, VIM, Snail, Twist, MT, MLH and down-regulation of Casp-3, PTEN, E-CAD, and BAX. The signaling pathways most commonly activated are KRAS, p53, TGF-β, TNF-α, WNT, NRF2 and AKT. This knowledge could potentially raise public awareness over the health risks faced by the human population living or working in a polluted environment and smokers. Human exposure to As and Cd should be minimize as much as possible. Healthcare policies targeting people belonging to these risk categories should include analysis of: DNA damage, oxidative stress, molecular alterations, and systemic level of heavy metals and of essential minerals. In this review, we present the literature regarding cellular and molecular alterations caused by exposure to As or Cd, focusing on the malignant transformation of normal epithelial cells after long-term intoxication with these two carcinogens.

KEYWORDS:

Arsenic; Breast cancer; Cadmium; Heavy metals; Prostate cancer; Risk factors

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