Combined effect of radiation and YM-881 (SMANCS) on murine tumors and bone marrow.
The combined effect of radiation and YM-881 (SMANCS) was studied in vitro and in vivo. When 0.25 microgram/ml of YM-881 was simultaneously combined with radiation, during and after irradiation for 30 min in total, Dq decreased from 3.3 Gy to 1.4 Gy without changing D0 in the dose-survival curve of exponentially growing SCC VII tumor cells. Five or ten times administrations of 0.1 mg/kg YM-881 at an interval of 24 h did not inhibit tumor growth. However, administration of 0.1 mg/kg YM-881 just before every irradiation which was repeated five times at an interval of 24 h yielded dose modifying factors (DMFs) of 1.8-1.2 when the tumor response to treatment was evaluated by the time for the tumors to regrow to three times the original volume. Administration of YM-881 ten times just before every irradiation yielded DMFs of 1.3-1.2. Adverse effects of the combination on bone marrow were examined by spleen colony assay. After five injections of 0.1 mg/kg YM-881, the mean number of CFU-S per femur decreased to 77% of the pretreatment level, but this was not significant statistically (0.1 greater than p greater than 0.05). The slope of radiation response curve for CFU-S per femur was not affected by the combination.
Ono
K
K
Department of Radiology, Faculty of Medicine, Kyoto University, Japan.
Wandl
E
E
Sasai
K
K
Tsutsui
K
K
Shibamoto
Y
Y
Takahashi
M
M
Abe
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005663:Furans / Q000494:pharmacology*; D008297:Male; D008299:Maleic Anhydrides / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D011137:Polystyrenes / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured; D009353:Zinostatin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity
D000903:Antibiotics, Antineoplastic; D005663:Furans; D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; D009353:Zinostatin