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Cited by 352Effects of Radiation ExposureMitochondrial Function and PathologyCell death mechanisms and regulation

Mitochondrial biogenesis and metabolic hyperactivation limits the application of MTT assay in the estimation of radiation induced growth inhibition

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Rai, Yogesh, Pathak, Richa, Kumari, Neeraj, Sah, Dhananjay Kumar, Pandey, Sanjay, Kalra, Namita, Soni, Ravi, Dwarakanath, B. S. +1 more·2018·Scientific Reports
DOI 10.1038/s41598-018-19930-wPMC PMC5784148
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Abstract

Metabolic viability based high throughput assays like MTT and MTS are widely used in assessing the cell viability. However, alteration in both mitochondrial content and metabolism can influence the metabolic viability of cells and radiation is a potential mitochondrial biogenesis inducer. Therefore, we tested if MTT assay is a true measure of radiation induced cell death in widely used cell lines. Radiation induced cellular growth inhibition was performed by enumerating cell numbers and metabolic viability using MTT assay at 24 and 48 hours (hrs) after exposure. The extent of radiation induced reduction in cell number was found to be larger than the decrease in MTT reduction in all the cell lines tested. We demonstrated that radiation induces PGC-1α and TFAM to stimulate mitochondrial biogenesis leading to increased levels of SDH-A and enhanced metabolic viability. Radiation induced disturbance in calcium (Ca 2+ ) homeostasis also plays a crucial role by making the mitochondria hyperactive. These findings suggest that radiation induces mitochondrial biogenesis and hyperactivation leading to increased metabolic viability and MTT reduction. Therefore, conclusions drawn on radiation induced growth inhibition based on metabolic viability assays are likely to be erroneous as it may not correlate with growth inhibition and/or loss of clonogenic survival.

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  • APOE4 astrocytes exhibit reduced mitochondrial metabolism as measured by MTT.

    “the APOE4 astrocytes exhibit reduced mitochondrial metabolism as measured by MTT20,36 (Fig. 5c)”

    From Altered mitochondrial dynamics and function in APOE4-expressing astrocytes (2020) · cites this paper as [20]

    The Introduction (page unavailable) says the MTT assay measures mitochondrial metabolic rate, supporting the use of MTT as a metabolic measure. The paper does not report a reduction in APOE4 astrocytes; its findings concern irradiated cells. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Rai, Y., Pathak, R., Kumari, N., Sah, D. K., Pandey, S., Kalra, N., Soni, R., Dwarakanath, B. S., & Bhatt, A. N.
Affiliations
Institute of Nuclear Medicine & Allied Sciences (IN)
Corresponding author
Bhatt, Anant Narayan
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-01-24
Volume
8
Issue
1
Pages
1531-1531
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-19930-w
PMC
PMC5784148
OpenAlex
W2791767507
Cited by
352
References
0
Citations by year
2026: 43 · 2025: 42 · 2024: 56 · 2023: 45 · 2022: 55 · 2021: 57 · 2020: 33 · 2019: 18 · 2018: 2
FWCI
18.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Indian Council of Medical Research
  • Defence Research and Development Organisation (311/1.4, INM 311)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
mitochondrial biogenesis, MTT assay, radiation-induced cell death, PGC-1α, TFAM, calcium homeostasis, clonogenic survival, cell growth inhibition
MeSH terms
Animals, Organelle Biogenesis, Cell Count, Cell Survival, Cells, Cultured, Cytological Techniques, Formazans, Humans, Metabolism, Radiation, Staining and Labeling, Tetrazolium Salts, Thiazoles, Mice

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