The radioprotective effect of 5-thio-D-glucose (5-TG, NSC 204984) on normal tissues of mice was investigated. The LD50 of 5-TG in A/J mice injected intraperitoneally (i.p.) is 5.5 g/kg. The animals were injected i.p. with saline or 5-TG followed by whole-body irradiation or localized irradiation of the foot. Mice injected with 1.5 g/kg of 5-TG were protected from gastrointestinal or bone marrow death following whole-body irradiation by a dose modification factor (DMF) of 1.1--1.3. The same dose of 5-TG protected mice from foot skin damage between days 0 and 40 post-irradiation by a DMF of 1.3, and from late foot deformity during days 60 to 90 post-irradiation by a DMF of 1.2. Foot skin reactions indicated that 5-TG provided maximal radioprotection up to 4 hours after an intraperitoneal injection. We have previously reported that 5-TG selectively kills and radiosensitizes hypoxic cells. Consequently, it may be possible to use this compound as an adjuvant to radiotherapy in order to kill or radiosensitize hypoxic cells and to radioprotect normal tissue.

Animals↗

PubMedDate not supplied

Comparison of the cytotoxicity of 5-thio-D-glucose and misonidazole on hypoxic cells in vitro.

The cytotoxicity of 5-thio-D-glucose (5-TG) and misonidazole (MISO) on hypoxic cells in vitro was compared, and the combined effect of these two compounds was investigated. The cytotoxicity of 5-TG on hypoxic SCK mammary carcinoma cells of mice was markedly greater than that of MISO. However, MISO was more toxic than was 5-TG to P815-X2 mastocytoma cells of mice. The elevation of temperature from 37.5 degrees C to 40.0 degrees C during incubation with drugs greatly enhanced the cell death. The thermal enhancement of cytotoxicity of 5-TG to mastocytoma cells appeared to be greater than that of MISO. Preliminary studies indicated that the combined effect of 5-TG and MISO is additive, suggesting the intracellular targets or cytocidal mechanisms of these two compounds may be different.

Adenocarcinoma↗

PubMedDate not supplied

Use of arsenic trioxide as an antivascular and thermosensitizing agent in solid tumors.

Arsenic trioxide, As2O3 (ATO), has been found to be an effective chemotherapeutic for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSaII tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5 to 42.5 degrees C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFalpha are noticeably increased in tumors 2 to 6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.

Angiogenesis Inhibitors↗