Radiosensitizing effect of nicotinamide and carbogen combined in fractionated pions or x-rays in SCCVII tumors.
Well-known radiotherapeutic strategies for hypoxic cells include hypoxic radiosensitizers, heavy particles, and fractionated irradiation. This study attempted to obtain the ultimate effectiveness of these strategies by combining nicotinamide plus carbogen (N + C) as a hypoxic radiosensitizer with fractionated pions. In addition, the influence on the N + C effect of X-ray dose rate used as a reference radiation was evaluated. When SCCVII tumors in the dorsum of feet reached 50 mm3 in volume, they were irradiated with pions (0.2 Gy/min), the same dose rate (LDR; 0.2 Gy/min) X-rays, or high dose rate (HDR; 1.5 Gy/min) X-rays in 10 fractions over 11 days. Nicotinamide (0.5 mg/g) was administered i.p. one hour before irradiation, and normobaric carbogen (95% oxygen and 5% carbon dioxide) was breathed from 10 min before irradiation. The effect was evaluated by tumor growth time (TGT50) assay. The combination of N + C significantly enhanced the effect of 30 Gy LDR and 28 Gy HDR X-rays, with the effect corresponding to that of 39 Gy HDR X-rays: the enhancement ratios were 1.2 and 1.4, respectively. The effect of 20 Gy pions was equivalent to the effect of 33 Gy HDR X-rays (ratio of 1.65), or the effect of N + C combined with 28 Gy HDR X-rays. However, N + C did not enhance the effect of 20 Gy pions. This suggested that the fractionated pions had great biological effectiveness against hypoxic cells. In conclusion, N + C afforded no additional benefit with fractionated pions, but it was thought to be of value for fractionated X-rays, even in a dose rate of 0.2 Gy/min.
Ohizumi
Y
Y
Department of Radiation Oncology, School of Medicine, Tokai University, Kanagawa, Japan.
Lam
G K
GK
Pickles
T
T
Fryer
C
C
Chaplin
D J
DJ
D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D015687:Cell Hypoxia; D005534:Foot Diseases / Q000532:radiotherapy; D007274:Injections, Intraperitoneal; D008651:Mesons / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D009536:Niacinamide / Q000008:administration & dosage / Q000627:therapeutic use*; D010100:Oxygen / Q000008:administration & dosage / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D012062:Relative Biological Effectiveness; D014964:X-Ray Therapy
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen