| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| Research Abstract |
1. The research on the competive radical reaction model for the radiation effect.
The rate equations for the competing reaction scheme of an intracelluler radiation were written and programmed for computer simulations of change in oxygen, thiol and electronaffinic sensitizer concentrations. A reaction scheme that also includes some non-radical target damage was also simulated. Simulations were made using available experimental data concerning intranuclear concentrations and reaction rate constants, respectively, K_o, K_s and K_i for the traget radical reactions to oxygen, glutathione (GSH) and misonidazole. Foward reaction rate constant K_o, K_s, K_i in the approximate ratio 10 ; 0.02 ; 0.4 satisfied the reaction scheme.
2. The research on the radiosensitizing effect for hypoxic sells.
The radiosensitizing effects on hypoxic cell sensitizer, misonidazole (MISO), in combination with D,L-buthione-S,R-sulfoximine (BSO), an inhibitor of GSH biosynthesis, were studied in NFSa tumors of C3H/He
… More
mice. When 5 mmole/Kg BSO was injected repeatedly 4 times at on interval of 6hr, GSH content in teh tumors decreased to 19% of the control 24hr after first injection of BSO. The radiosensitizing effect of 0.5mmole/Kg MISO was markedly increased by this BSO treatment. The enhancement ratio (ER) of this combined treatment was 1.93. On the other hand, ERs of 1.44 and 1.16 were obtained for MISO (0.5 mmole/Kg) and for 4 injections of BSO (5 mmole/Kg) in combination with radiation, respectively.
3. The research on normal tissues.
1) The GSH contents in C3H/He mouse normal tissues were assayed by high performance liquid chromatography.
2) The increase of reactions in spontanous and artificial hypoxic skin of ICR mouse hind leg were specifically observed with increasing MISO dose (50 - 800 mg/kg). The radiation sensitization of hypoxic skin by MISO was enhanced by the combination with BSO (1.1 kg, 4 times every 12hr) by a factor ca. 8. No enhancement of radiation response for eaorix skin with durgs.
A considerable increase in the efficiency with MISO in combination with BSO was found, more studies on toxicities are however needed to get a definite conclusion Less
|
