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Subchronic exposure to low-level lanthanum, cerium, and yttrium mixtures altered cell cycle and increased oxidative stress pathways in human LO‑2 hepatocytes but did not cause malignant transformation

  • Qinxin Liu
    ,
  • Zhiqiang Jiang
    ,
  • Meiyue Qiu
    ,
  • Melvin E. Andersen
    ,
  • James Crabbe
    ,
  • Xia Wang
  • Fudan University
    ,
  • ScitoVation LLC
    ,
  • University of Oxford
    ,
  • Qingdao University
Research Output:
Contribution to journal
Article
 Peer-review

Open access

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

Abstract

Human exposures to rare earth elements are increasing with expanded use in aerospace, precision instruments, and new energy batteries, materials, and fertilizers. Individually these elements have low toxicity, although few investigations have examined the health effects of longer-term mixture exposures. We used the LO-2 cell line to examine the effects of graded exposures to lanthanum, cerium, and yttrium (LCY) mixtures at 1-, 100-, and 1000-fold their human background levels (0.31 μg/L La, 0.25 μg/L Ce, and 0.12 μg/L Y) on cell cycle, oxidative stress, and nuclear factor erythroid-2-related factor (NRF2) pathway biomarkers, assessing responses every 10 passages up to 100 passages. Cell migration, concanavalin A, malignant transformation, and tumorigenesis in nude mice were also examined. Mixed LCY exposures activated oxidative stress and the NRF2 pathway by the 30th passage and increased the proportion of cells in the S phase and cell cycle-specific biomarkers by the 40th passage. LCY exposures did not cause malignant transformation of hepatocytes or induced tumorigenesis in nude mice but enhanced cell proliferation, migration, and agglutination. Importantly, LCY mixtures with longer-term exposure activated the NRF2 pathway and altered the hepatocyte cell cycle at doses far below those used in previous toxicological studies. The consequences of LCY mixtures for public health merit further study.

Publication Information

Output type

Research Output:
Contribution to journal
Article
 Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 22002-22013 (12 pages)

Journal (Volume, Issue Number)

Environmental Science and Technology (Volume 58, Issue 50)

Publication milestones

  • Accepted/In press - 22/11/2024
  • Published - 04/12/2024

Publication status

Published - 04/12/2024

ISSN

0013-936X

Publication IDs

  • handle.net: 10547/626515
  • Scopus: 85211191909

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