Sarcoma-180 cells and human colorectal tumor cells under in vitro hypoxic conditions are more sensitive to mitomycin C and carboquone.
The effects of oxygen concentration on the chemosensitivity of mouse sarcoma-180 (S-180) cells and human colorectal cancer tissues to mitomycin C (MMC) or carboquone (CQ) were determined in vitro, since evidence had been obtained that these drugs are more effective in HeLa cells. The results were as follows: (a) S-180 cells exposed to various concentrations of MMC or CQ for 2 h under conditions of normal aeration (about 20%) or hypoxia (5.0% and 0%) were then maintained under normal conditions of aeration for 3 days. Change of viability was assessed by succinate dehydrogenase (SD) activity. With exposure of the cells to MMC or CQ, under anoxic conditions (O2:0%), SD activity decreased to a greater extent than seen in the control cells. The value for CQ was from 61.5% to about 36.2%. (b) The decrease in the SD activity of 20 colorectal cancer tissues kept under conditions of anoxia was compared with findings under normally aerated conditions, following exposure to 30 microM of MMC or 1.6 microM of CQ. On exposure to MMC or CQ under anoxic conditions, SD activity decreased significantly, compared with normally aerated conditions (P less than 0.001 for MMC; P less than 0.05 for CQ). As colorectal cancer is less sensitive than other tissues to various chemotherapeutic agents, we recommend that MMC and CQ be prescribed to treat patients with these malignant lesions.
Kusumoto
T
T
Cancer Center of Kyushu University Hospital, Fukuoka, Japan.
Maehara
Y
Y
Sakaguchi
Y
Y
Kohnoe
S
S
Emi
Y
Y
Sugimachi
K
K
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002225:Carbazilquinone / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008297:Male; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000201:enzymology; D013385:Succinate Dehydrogenase / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D008937:Mitomycins; D002225:Carbazilquinone; D016685:Mitomycin; D013385:Succinate Dehydrogenase