| Popis: |
INTRODUCTION: Fluoroacetate (FA) is a highly toxic metabolic poison found in eight species of plants – including Dichapetalum and Gastrolobium - growing in Australia, South and Central Africa and South America. The level of FA in some plants can reach up to 5 g kg-1 dry weight and can cause death of livestock and domestic animals. Moreover, FA can be found in fog and rain-drops in some industrial regions. The best known representative of FA is its sodium salt (SFA, compound 1080), which is used in several countries for controlling populations of some vertebrates. Although extremely toxic, FA has positive properties: it can prevent development of tolerance to morphine, and has radioprotective power due to its capacity to reduce body temperature and oxygen consumption. OBJECTIVES: To evaluate the antitumor properties of SFA in monotherapy regime and in combination with a known antitumor compound. MATERIALS AND METHODS: Mice bearing Ehrlich tumor carcinoma were treated daily with SFA, 1.25mg/kg intraperitoneally. SHR mice with benzo[a]pyrene induced sarcoma were administered a single dose of cyclophosphamide and SFA daily, 1mg/kg intraperitoneally or 2mg/kg via drinking water. RESULTS AND DISCUSSION: SFA significantly inhibited growth of Ehrlich tumor carcinoma. In experiments with autochthonous induced by benzo[a]pyrene subcutaneous tumors, SFA exhibited enhancement of antitumor effect of cyclophosphamide (CP), significantly increasing the number of mice with stabilized or decreased tumor volume. Comparison of antitumor activity of SFA and metformin showed that neither compound has significant effect being administered in a monotherapy regimen, though both enhance the effect of CP increasing the number of mice with stabilized or decreased tumor volume. In contrast to metformin, SFA extended the average duration of the effect. CONCLUSION: The data provides a basis for studies on the mechanism of the antitumor effect of SFA, and for evaluating other combinations of SFA with known antitumor compounds. |
