In vivo study of radiosensitizing effect of hypoxic cell radiosensitizer PR-350 on a human small cell lung cancer.

摘要

PURPOSE: 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 AND MATERIALS: 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. CONCLUSION: 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.