Lithium promotes malignant transformation of nontumorigenic cells in vitro

Makoto Sudo; Kazunori Hashimoto; Masafumi Yoshinaga; Mohammad Daud Azimi; Said Hafizullah Fayaz; Nobuyuki Hamajima; Lisa Kondo-Ida; Kiyoshi Yanagisawa; Masashi Kato

doi:10.1016/j.scitotenv.2020.140830

Lithium promotes malignant transformation of nontumorigenic cells in vitro

Sci Total Environ. 2020 Nov 20:744:140830. doi: 10.1016/j.scitotenv.2020.140830. Epub 2020 Jul 14.

Authors

Makoto Sudo¹, Kazunori Hashimoto², Masafumi Yoshinaga¹, Mohammad Daud Azimi³, Said Hafizullah Fayaz⁴, Nobuyuki Hamajima⁵, Lisa Kondo-Ida⁶, Kiyoshi Yanagisawa⁷, Masashi Kato⁸

Affiliations

¹ Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Voluntary Body, International Health Care in Universities, Nagoya, Japan.
³ Department of Human Resources, Ministry of Public Health, Kabul, Afghanistan.
⁴ Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Administrative Office of the President, Deputy Public Relations and Outreach, Kabul, Afghanistan.
⁵ Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁶ Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Molecular and Cancer Medicine, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
⁷ Department of Molecular and Cancer Medicine, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
⁸ Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Voluntary Body, International Health Care in Universities, Nagoya, Japan; Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan. Electronic address: katomsasa@med.nagoya-u.ac.jp.

PMID: 32721671
DOI: 10.1016/j.scitotenv.2020.140830

Abstract

Because of the deficiency of water caused by the regional disparities of rainfall due to global warming, attention has been given to the use of well water as drinking water in developing countries. Our fieldwork study in Afghanistan showed that there was a maximum value of 3371 μg/L and an average value of 233 μg/L of lithium in well drinking water. Since the level of lithium in well water is higher than the levels in other countries, we investigated the health risk of lithium. After confirming no influence of ≤1000 μM lithium on cell viability, we found that lithium at concentrations of 100 and 500 μM promoted anchorage-independent growth of human immortalized keratinocytes (HaCaT) and lung epithelial cells (BEAS-2B) but not that of human keratinocytic carcinoma cells (HSC-5) or lung epithelial carcinoma cells (A549). The same concentrations of lithium also promoted phosphorylation of c-SRC and MEK/ERK but not that of AKT in the keratinocytes. Inhibitors of c-SRC (PP2) and MEK (PD98059) suppressed the lithium-induced increase in anchorage-independent growth of the keratinocytes. Our results suggested that lithium promoted transformation of nontumorigenic cells rather than progression of tumorigenic cells with preferential activation of the c-SRC/MEK/ERK pathway. Since previous pharmacokinetics studies indicated that it is possible for the serum level of lithium to reach 100 μM by drinking 2.5 L of water containing 3371 μg/L of lithium per day, the high level of lithium contamination in well drinking water in Kabul might be a potential oncogenic risk in humans.

Keywords: Afghanistan; Drinking water; Lithium; Oncogenesis; Progression; Transformation.

MeSH terms

Afghanistan
Cell Line
Cell Transformation, Neoplastic*
Humans
Keratinocytes
Lithium*

Substances

Lithium