title: Effects of antineoplastic agents and hyperthermia on cytotoxicity toward chronically hypoxic glioma cells.
abstract: The effects of hyperthermia and antineoplastic agents on the cytotoxicity to normally oxygenated and chronically hypoxic glioma cells were investigated in vitro. Exposure to temperatures above 43.0 degrees C was less cytotoxic to hypoxic cells which predominantly accumulated in the G0/G1 phase fraction. On the other hand, mitomycin C (MMC) and adriamycin (ADM) were preferentially cytotoxic to hypoxic cells not only at 37 degrees C but also at elevated temperatures (42 degrees C and 43 degrees C). These two agents showed marked synergistic effects with hyperthermia under both oxygenated and hypoxic conditions. In contrast, bleomycin (BLM), cis-diamminedichloroplatinum(II) (CDDP), and vincristine (VCR) were preferentially cytotoxic to oxygenated cells at both 37 degrees C and elevated temperatures. CDDP showed cytotoxic synergism with hyperthermia that appeared to be oxygen-dependent. A nitrosourea derivative, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), showed no major preferential toxicity under either oxygenated or hypoxic conditions. This study suggests that hyperthermia in combination with MMC or ADM would have a greater cytotoxic effect on hypoxic cell subpopulations of malignant gliomas.
authors.affiliation: Department of Neurosurgery, Niigata University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: R
authors.initials: R
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Hondo
authors.forename: M
authors.initials: M
authors.lastname: Kuroki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D005910:Glioma / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents