2024-03-28T09:00:30Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00031434
2023-01-16T04:24:59Z
499:500:501
Lithium promotes malignant transformation of nontumorigenic cells in vitro
Sudo, Makoto
103681
Hashimoto, Kazunori
103682
Yoshinaga, Masafumi
103683
Azimi, Mohammad Daud
103684
Fayaz, Said Hafizullah
103685
Hamajima, Nobuyuki
103686
Kondo-Ida, Lisa
103687
Yanagisawa, Kiyoshi
103688
Kato, Masashi
103689
Afghanistan
Drinking water
Lithium
Oncogenesis
Progression
Transformation
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.
ファイル公開:2022-11-20
journal article
Elsevier
2020-11-20
application/pdf
Science of The Total Environment
744
140830
0048-9697
https://nagoya.repo.nii.ac.jp/record/31434/files/SCIENCE_OF_THE_TOTAL_ENVIRONMENT_2020_744_140830.pdf
eng
https://doi.org/10.1016/j.scitotenv.2020.140830
© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/