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Studies with bleomycin and misonidazole on aerated and hypoxic cells
Open accessAbstract
Bleomycin is a chemotherapuetic drug used primarily in the treatment of squamous-cell carcinoma, while misonidazole is an effective radiosensitizer and potent cytotoxic agent selectively affecting hypoxic cells. V79 Chinese hamster cells were used to investigate the cytotoxicity of bleomycin (BLM) under aerated and hypoxic conditions as a function of drug concentration. At a lowered temperature of 17.5 degrees C, or at an elevated temperature of 42.5 degrees C, hypoxic cells are more sensitive to killing by BLM than aerated cells. At either of these temperatures, progression through the cell cycle is inhibited. However, at 37.5 degrees C, mimicking a clinical situation, the sensitivies are reversed, and hypoxic cells are appreciably more resistant. Although many factors are involved, the major reason for this is that aerated cells are cycling while hypoxic cells are not. Aerated cells can progress into phases of the cell cycle where they are more sensitive to killing by BLM. Misoinidazole (=Ro-07-0582) was used in combination with BLM, since its mode of action has been shown to be psecific for killing hypoxic cells. It concomitant use with BLM could be of potential use in chemotherapy when confronted with the hypoxic cell component of solid tumours.
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“It has been known since the 1950s that hypoxia is a crucial mediator of chemo-and radioresistance (Gray et al., 1953;Roizin-Towle & Hall, 1978).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Roizin-Towle & Hall, 1978
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Metadata
- Authors
- Roizin-Towle, L., & Hall, E. J.
- Affiliations
- Columbia University (US)
- ORCID
- Hall, E J
- Venue
- British Journal of Cancer
- Published
- 1978-02
- Volume
- 37
- Issue
- 2
- Pages
- 254-260
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2009591
- OpenAlex
- W2054043592
- Cited by
- 63
- References
- 20
- Citations by year
- 2025: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2016: 1 · 2015: 3 · 2012: 3
- FWCI
- 5.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- British Journal of Cancer (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Physical Sciences › Physics and Astronomy › Radiation › Radiation Therapy and Dosimetry
- Keywords
- bleomycin, misonidazole, hypoxic cells, radiosensitizers, V79 cells, cell cycle progression, solid tumors, squamous cell carcinoma
- MeSH terms
- Hypoxia, Bleomycin, Cell Line, Cell Survival, Dose-Response Relationship, Drug, Nitroimidazoles, Oxygen, Temperature
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