Kokubun M, Fujimoto S, Shrestha R D, Ohta M, Kobayashi K, Kiuchi S, Konno C, Fujita M, Taguchi T, Okui K
First Dept. of Surgery, School of Medicine, Chiba University.
Gan To Kagaku Ryoho. 1989 Mar;16(3 Pt 1):371-7.
For the purpose to analyse the influence of a thermosensitizing drug, misonidazole (MIS), on tissue oxygen tension (TpO2), TpO2 in human gastric cancer tissue (H-23) was measured by a polarographic method. MIS, 500 mg/kg, was given i.p. and then the heat treatment was done in a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. A second treatment was performed to develop thermotolerance at the following intervals: 24 hours, 72 hours, 5 days, and 7 days. Tumor doubling time was shortest at 72-hour interval, i.e., the maximal thermotolerance of the tumor developed at 72-hour interval, whereas the tumor doubling time in case of combined use of MIS was shortest at 24-hour interval. TpO2 in the 72-hour interval treatment decreased soon after hyperthermia, and returned to a pre-heated value 3 hours after, whereas in the other 3 treatments the recovery time was 6 to 12 hours. On the other hand, in 24-hour interval of the combined use of MIS, the post-thermal value of TpO2 was about a half of the pre-thermal value and recovered 24 hours after. In the 5- and 7-day interval treatments, TpO2 declined notably and did not return to the pre-thermal value during 24 hours. These data suggest that the thermo-sensitizing effects of MIS were brought about by prolonged and extreme decrease in TpO2.
