In vivo study of radiosensitizing effect of hypoxic cell radiosensitizer PR-350 on a human small cell lung cancer.
OBJECTIVE
The purpose of this study was to clarify the utility of 1-(1',3',4'-Trihydroxy-2'-Butoxy) Methyl-2-Nitroimidazol (PR-350) as a hypoxic cell radiosensitizer in an in vivo human tumor. We examined the effect of PR-350 on the changes of tumor volume and microscopic features following irradiation.


METHODS
Tissue from a human small-cell lung cancer was transplanted to 136 nude mice. They were given 200 mg/kg of PR-350, as a hypoxic cell radiosensitizer, or saline, for the control. One hundred mice were used to evaluate the effect of PR-350 on tumor volume after irradiation, and the other mice were used for histological study: hematoxylin and eosin staining, immunohistochemistry (Ki-67 and p53), TUNEL staining, and electromicroscopy.


RESULTS
Respective 10, 15, and 20 Gy irradiation groups showed some tendency of a sensitizing effect of PR-350, compared with the saline group. A statistically significant difference was observed between PR-350- and saline-treated groups with 15 Gy of irradiation (p < 0.05). Apoptotic cells counts were slightly increased in both PR-350 and saline groups at 6 h after 15 Gy of irradiation. Massive necrotic areas were noted in both groups at 72 h after irradiation. p53 was intensely positive in most tumor cells with or without irradiation. However, no significant difference was found between PR-350 and saline groups in these microscopic features.


CONCLUSIONS
PR-350 was an effective hypoxic cell radiosensitizer for a human small cell lung cancer in vivo, in which necrotic change was dominant following irradiation.
Suzuki
Y
Y
Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Japan.
Hasegawa
M
M
Hayakawa
K
K
Mitsuhashi
N
N
Niibe
H
H
D000818:Animals; D018288:Carcinoma, Small Cell / Q000473:pathology / Q000532:radiotherapy* / Q000648:ultrastructure; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D000860:Hypoxia; D007093:Imidazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D008875:Middle Aged; D009336:Necrosis; D009368:Neoplasm Transplantation; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013997:Time Factors
D007093:Imidazoles; D011838:Radiation-Sensitizing Agents; C106738:doranidazole