Hyperthermia enhances the cytotoxicity against hypoxic cells of RP-170, a new 2-nitroimidazole nucleoside hypoxic cell sensitizer.
The effect of the new hypoxic cell sensitizer, 1-[2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl-2-nitroimidazole (RP-170), combined with heat against EMT6/KU cells, was determined under conditions of in vitro hypoxia. Heat-induced cytotoxicity for the EMT6/KU cells was increased to a greater extent under conditions of hypoxia and a normal pH of the medium. Hypoxia also reduced the surviving fraction of the cells treated either with RP-170 alone or with RP-170 plus heat. The concomitant treatment of RP-170 and heat inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia in all experimental groups, with a significant difference (p < 0.05). Therefore, RP-170 combined with exposure to heat may be an effective treatment for hypoxic cells in a solid tumor, as these cells are resistant to radiation and/or to many chemotherapeutic agents.
Emi
Y
Y
Cancer Center, Kyushu University Hospital, Fukuoka, Japan.
Maehara
Y
Y
Kusumoto
T
T
Baba
H
H
Sakaguchi
M
M
Sugimachi
K
K
D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006358:Hot Temperature; D051379:Mice; D008807:Mice, Inbred BALB C; D008920:Misonidazole / Q000494:pharmacology; D009593:Nitroimidazoles / Q000494:pharmacology*; D009705:Nucleosides / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009593:Nitroimidazoles; D009705:Nucleosides; D011838:Radiation-Sensitizing Agents; C060996:RP 170; D008920:Misonidazole