Abstract
The effect of oral administration of diazoxide on rats bearing mammary carcinomas induced by dimethylbenzanthracene (7,12‐DMBA) or methylnitro sourea (MNU) was investigated. Administration of 300 mg/kg diazoxide caused mild reversible diabetes with maximum glucose levels of 305 ± 74 (control: 119 ± 12) mg/dl and related insulin levels of 15 ± 5 (control: 24 ± II) μ U/ml after 4 hr in tumor‐bearing animals. Following the same dose of diazoxide a more than 90% inhibition of tumor growth was observed in 7, 12‐DMBA‐ and MNU‐induced autochthonous rat mammary carcinomas as well as remission of the median total tumor volume per group in 7, 12‐DMBA‐induced lesions. Frequency, onset of remissions and median remission duration proved to be dose‐dependent in 7,12‐DMBA‐induced mammary carcinoma and, with the exception of the median remission duration, in MNU‐induced tumors too. After cessation of diazoxide application, 30% rebound responses were observed in 7, 12‐DMBA‐induced tumors of animals that had had a first remission due to diazoxide. Application of insulin (2 IU per rat) together with diazoxide (300 mg/kg) reversed the tumor‐inhibiting effect of diazoxide in MNU‐induced tumors. The diazoxide effect might in part be due to a decrease in the percentage of proliferating cells caused by insulin depletion as indicated by a lower amount of cells in S‐phase, as measured by DNA‐flow cytometry. Marked toxicity was observed after effective doses of diazoxide; the experiments indicate that induction of reversible diabetes might be a useful tool in the treatment of hormone‐dependent mammary carcinoma.