In vitro testing of chemosensitivity in physiological hypoxia.
Highly aggressive, rapidly growing tumors are often hypoxic, owing to an inadequate supply relative to consumption of oxygen (O2) in the expanding tumor mass, or growth in tissues with physiologically low O2 concentrations (such as bone marrow). Selection of tumor cells that can grow or survive under hypoxic conditions appears from both experimental and clinical studies to impact tumor progression, response to therapy, and to increase resistance to radiation and to certain cytotoxic drugs. Therefore, the predictive value of preclinical testing of anticancer agents in cell culture might be improved by conducting testing in conditions of physiological hypoxia. We review the impact of hypoxia on anticancer drug cytotoxicity and the methods used in our laboratory to asses the cytotoxic activity of single antineoplastic drugs under conditions of physiological hypoxia.
Grigoryan
Rita
R
Developmental Therapeutics Section, Children's Hospital of Los Angeles, Los Angeles, CA, USA.
Keshelava
Nino
N
Anderson
Clarke
C
Reynolds
C Patrick
CP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002245:Carbon Dioxide; D010100:Oxygen