Effects of cell density on drug-induced cell kill kinetics in vitro (inoculum effect)
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The effects of cell density on drug-induced cell kill kinetics were studied by means of clonogenic assay using 3 human leukaemia-lymphoma cell lines. Mitoxantrone, daunorubicin, doxorubicin, vincristine and bleomycin were progressively less efficacious when cell density increased (positive inoculum effects), whereas the effects of cis-platin and carboplatin were not influenced by cell density. Inoculum effects were related to the kind of chemotherapeutic agents tested, irrespective of the type of cell lines used. Preincubation of mitoxantrone or doxorubicin in the presence of cells in high density resulted in decreases in the cytocidal activity, whereas the effects of bleomycin, vincristine and cis-platin were unaffected. These results show that cell density affects the biological effect of certain chemotherapeutic agents. Inactivation of drugs by high densities of cells partially explains this phenomenon.
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The density of eukaryotic cells can have a profound influence on the outcome of toxicological studies.
“it soon became apparent that the density of eukaryotic cells can have a profound influence on the outcome of toxicological studies (Ohnuma et al., 1986; Brook, 1989; Schildknecht et al., 2009; Schildknecht et al., 2011; Scholz et al., 2011).”
From In Vitro research Reproducibility: Keeping up High Standards (2019) · cites this paper as Ohnuma et al., 1986
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In Vitro research Reproducibility: Keeping up High Standards
Hirsch, C., & Schildknecht, S. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01484 · Cited by 161 · see citing works
- Authors
- Ohnuma, T., Arkin, H., & Holland, J. F.
- Venue
- British Journal of Cancer
- Published
- 1986-09
- Volume
- 54
- Issue
- 3
- Pages
- 415-421
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2001630
- OpenAlex
- W1993176032
- Cited by
- 44
- References
- 0
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2012: 1
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- British Journal of Cancer (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 15936, CA-25865)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- inoculum effect, cell density, clonogenic assay, mitoxantrone, daunorubicin, doxorubicin, vincristine, bleomycin, cisplatin, carboplatin, anticancer agents
- MeSH terms
- Antineoplastic Agents, Bleomycin, Burkitt Lymphoma, Cell Count, Cell Survival, Cisplatin, Daunorubicin, Dose-Response Relationship, Drug, Doxorubicin, Humans, Leukemia, Lymphoid, Leukemia, Myeloid, Mitoxantrone, Organoplatinum Compounds, Vincristine, Carboplatin
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