Mercury and cancer: Where are we now after two decades of research?

Anatoly V Skalny, Michael Aschner, Marina I Sekacheva, Abel Santamaria, Fernando Barbosa, Beatriz Ferrer, Jan Aaseth, Monica M B Paoliello, Joao B T Rocha, Alexey A Tinkov

Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2022;164():113001

PMID: 35447290

Full Text on Elsevier Science View on PubMed

Abstract

The present study aims to review epidemiological and experimental toxicology studies published over the last two decades linking mercury (Hg) exposure and carcinogenesis, with a special emphasis on the potential underlying mechanisms. While some epidemiological studies have observed a strong association between environmental/occupational Hg exposure levels, measured in blood, toenail, and hair, and cancer risk and mortality, others failed to reveal any association. In experimental models, high-dose Hg exposure has been linked with cytotoxicity, whereas low-dose exposure was posited to induce proliferative responses in both normal and cancerous cells by interference with estrogen receptor, ERK1/2, JNK, NADPH-oxidase and, potentially, Nrf2 signaling. Combined with reduced apoptosis and pro-survival signaling upon low-dose Hg exposure, accumulation of DNA lesions in cells may predispose to an increased risk of malignant transformation. In addition, the pro-oxidant activity of Hg species may induce oxidative DNA modifications and inhibits DNA repair mechanisms. Furthermore, epigenetic effects of Hg exposure seem to contribute to the carcinogenic activity, although the particular mechanisms have yet to be characterized. Therefore, even after 20 years of research, one cannot consider Hg as a non-carcinogenic agent, whereas specific mechanisms of Hg-induced toxicity may promote carcinogenic risk.

Address: World-Class Research Center "Digital Biodesign and Personalized Healthcare", IM Sechenov First Moscow State Medical University (Sechenov University), 119435, Moscow, Russia.; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.; Laboratorio de Aminoácidos Excitadores/Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía, Mexico City, 14269, Mexico.; Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto, Brazil.; Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, N-2624, Lillehammer, Norway; Research Department, Innlandet Hospital, P.O. Box 104, N-2381, Brumunddal, Norway.; Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.; Laboratory of Molecular Dietetics, IM Sechenov First Moscow State Medical University, Moscow, 119146, Russia; Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, 150003, Yaroslavl, Russia. Electronic address: [email protected].

DOI: 10.1016/j.fct.2022.113001