Collaborative Study of Thresholds for Mutagens: Hormetic Responses in Cell Proliferation Tests Using Human and Murine Lymphoid Cells.

aclarubicin adaptive response ethyl methanesulfonate hormesis hygromycin mitomycin C

Journal

Dose-response : a publication of International Hormesis Society
ISSN: 1559-3258
Titre abrégé: Dose Response
Pays: United States
ID NLM: 101308899

Informations de publication

Date de publication:
Historique:
received: 13 02 2021
revised: 21 05 2021
accepted: 09 06 2021
entrez: 15 7 2021
pubmed: 16 7 2021
medline: 16 7 2021
Statut: epublish

Résumé

We previously showed that hormetic responses can be established in cell activity tests using human and murine adherent cells. This time, we examined whether hormetic responses can be established in cell proliferation tests using suspended human and murine lymphoid cells. Human lymphoblastoid cells (TK6) and mouse lymphoma cells (L5178Y) were cultured in multi-well culture plates and treated with mitomycin C, ethyl methansulfonate, hygromycin B, aclarubicin or colchicine at various dose levels and the number of cells was measured at varied times using a flow cytometer. When the ratio of the number of cells treated with a test chemical to those in the negative control was plotted, the dose-response relationship typically showed a reverse U-shaped curve, indicating the occurrence of hormesis and existence of thresholds in cell toxicity. The hormetic responses depended largely on the test chemical, dose level and exposure time. When examining responses over the course of time, a J-shaped or fallen S-shaped curve was also observed. The dose-response relationship showed a reverse U-shaped curve, a hallmark of hormesis, at least some time points for all chemicals tested here, indicating that chemical hormesis can be established in in vitro cell proliferation tests.

Sections du résumé

BACKGROUND BACKGROUND
We previously showed that hormetic responses can be established in cell activity tests using human and murine adherent cells. This time, we examined whether hormetic responses can be established in cell proliferation tests using suspended human and murine lymphoid cells.
METHODS METHODS
Human lymphoblastoid cells (TK6) and mouse lymphoma cells (L5178Y) were cultured in multi-well culture plates and treated with mitomycin C, ethyl methansulfonate, hygromycin B, aclarubicin or colchicine at various dose levels and the number of cells was measured at varied times using a flow cytometer.
RESULTS RESULTS
When the ratio of the number of cells treated with a test chemical to those in the negative control was plotted, the dose-response relationship typically showed a reverse U-shaped curve, indicating the occurrence of hormesis and existence of thresholds in cell toxicity. The hormetic responses depended largely on the test chemical, dose level and exposure time. When examining responses over the course of time, a J-shaped or fallen S-shaped curve was also observed.
CONCLUSIONS CONCLUSIONS
The dose-response relationship showed a reverse U-shaped curve, a hallmark of hormesis, at least some time points for all chemicals tested here, indicating that chemical hormesis can be established in in vitro cell proliferation tests.

Identifiants

pubmed: 34262412
doi: 10.1177/15593258211028473
pii: 10.1177_15593258211028473
pmc: PMC8246511
doi:

Types de publication

Journal Article

Langues

eng

Pagination

15593258211028473

Informations de copyright

© The Author(s) 2021.

Déclaration de conflit d'intérêts

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Auteurs

Shizuyo Sutou (S)

School of Pharmacy, Shujitsu University, Naka-ku, Okayama-shi, Okayama-ken, Japan.

Akiko Koeda (A)

Ina Research Inc., Ina-shi, Nagano-ken, Japan.

Kana Komatsu (K)

Ina Research Inc., Ina-shi, Nagano-ken, Japan.

Toshiyuki Shiragiku (T)

Tokushima Research Institute, Otsuka Pharmaceutical Co, Ltd, Tokushima-shi, Tokushima-ken, Japan.

Hiroshi Seki (H)

Safety Studies Section, BML Inc, Kawagoe-shi, Saitama-ken, Japan.

Toshiyuki Kudo (T)

School of Pharmacy, Shujitsu University, Naka-ku, Okayama-shi, Okayama-ken, Japan.

Classifications MeSH