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Updated: Aug 14, 2026
An Orthotopic Model of Murine Bladder Cancer
Published on: February 6, 2011
Influence of misonidazole on the radiosensitivity of transplantable transitional cell bladder carcinoma in mice
Abstract:
The radiosensitizing properties of misonidazole (Ro-07-0582; NSC-26137) were evaluated in a leg transplanted model of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) induced transitional cell bladder carcinoma in C3H/He mice. Animals bearing tumor received fractionated radiation of 400 rads X 5 or 600 rads X 5. Other groups with the same radiation doses were treated with misonidazole (0.75 mg per g) before each radiation fraction. Radiation alone was effective in prolonging Mean Survival Time, 17 per cent for 400 rads X 5 and 45 per cent for 600 X 5, with an associated delay in tumor growth. Misonidazole in the 600 rads X 5 group showed a radiosensitizing effect by further slowing tumor growth and prolonging Mean Survival Time by 80 per cent over the control and 24 per cent over radiation alone. Misonidazole alone did not show notable cytotoxic effects.
Insights
Misonidazole enhances radiation therapy for bladder cancer in mice. This drug, when combined with radiation, significantly slowed tumor growth and improved survival rates in preclinical models.
Area of Science:
- Oncology
- Radiation Oncology
- Pharmacology
Background:
- Transitional cell bladder carcinoma is a significant health concern.
- N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) is a known inducer of bladder cancer in animal models.
- Misonidazole is an investigational hypoxic cell radiosensitizer.
Purpose of the Study:
- To evaluate the radiosensitizing potential of misonidazole in a mouse model of bladder cancer.
- To determine the effect of misonidazole combined with fractionated radiation on tumor growth and survival.
Main Methods:
- A leg transplanted model of FANFT-induced transitional cell bladder carcinoma in C3H/He mice was used.
- Animals received fractionated radiation (400 or 600 rads x 5) with or without misonidazole (0.75 mg/g).
- Tumor growth delay and Mean Survival Time (MST) were measured.
Main Results:
- Radiation alone significantly prolonged MST and delayed tumor growth.
- Misonidazole demonstrated a radiosensitizing effect when combined with 600 rads x 5 radiation, further slowing tumor growth.
- The combination therapy resulted in an 80% increase in MST over controls and a 24% increase over radiation alone.
- Misonidazole alone did not exhibit significant cytotoxic effects.
Conclusions:
- Misonidazole acts as a radiosensitizer in this preclinical model of bladder cancer.
- The combination of misonidazole and fractionated radiation shows promise for improving treatment outcomes.
- Further investigation into misonidazole as an adjunct to radiation therapy for bladder cancer is warranted.
