Effects of alpha-difluromethylornithine on the development of deeply invasive urinary bladder carcinomas in mice
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S Samma1, K Uchida, J Seidenfeld
1Department of Pathology, Northwestern University Medical School, Chicago, IL.
Abstract:
alpha-Difluoromethylornithine (DFMO), was examined for its ability to suppress the development of invasive urinary bladder carcinoma in C3H/He male mice. Continuous administration of 0.2% DFMO in water following carcinogen treatment (0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine, BHBN, in drinking water for 8 weeks) was effective in suppressing urinary bladder carcinomas (P less than 0.05) as compared with the control group. However, when comparison was made based on tumors involving the entire urinary tract, protective effects could not be demonstrated. Coadministration of DFMO (0.2%) and BHBN (0.01%) did not alter tumor induction by the latter. These results were in sharp contrast to the protective effects in rats. Since bladder tumors in rats are of low grade and superficial whereas those in mice are of high grade and deeply invasive, our data indicate that DFMO has little to no effects against the development of aggressive forms of bladder carcinoma.
Insights
Alpha-difluoromethylornithine (DFMO) showed limited effectiveness in preventing aggressive, invasive urinary bladder cancer in mice. The drug did not prevent tumor development when administered with the carcinogen, suggesting it is ineffective against advanced bladder carcinoma.
Area of Science:
- Oncology
- Urology
- Chemoprevention
Background:
- Urinary bladder carcinoma poses a significant health challenge.
- Alpha-difluoromethylornithine (DFMO) has shown promise in chemoprevention studies.
- Investigating DFMO's efficacy against aggressive bladder cancer is crucial.
Purpose of the Study:
- To evaluate the chemopreventive potential of DFMO against invasive urinary bladder carcinoma in a mouse model.
- To determine if DFMO can suppress tumor development induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN).
Main Methods:
- C3H/He male mice were administered 0.05% BHBN in drinking water for 8 weeks to induce bladder tumors.
- Continuous administration of 0.2% DFMO in drinking water was initiated post-carcinogen treatment.
- Tumor incidence and invasiveness were assessed and compared to control groups.
Main Results:
- Continuous DFMO administration significantly suppressed the development of urinary bladder carcinomas (P < 0.05) compared to controls.
- However, DFMO did not demonstrate protective effects against tumors involving the entire urinary tract.
- Coadministration of DFMO and BHBN did not alter tumor induction rates.
Conclusions:
- DFMO exhibits limited efficacy against the development of aggressive, deeply invasive forms of urinary bladder carcinoma in mice.
- The observed effects contrast with protective effects seen in rats, likely due to differences in tumor grade and invasiveness.
- DFMO may not be a suitable chemopreventive agent for aggressive bladder cancers.