ABSTRACT
Traces of pesticides imazalil, cypermethrin and carbendazim are detected in plants used for human consumption. To explore whether their application in oral combinations will induce DNA breaks in hepatocytes, a subchronic in vivo experiment was performed in Swiss mice. Doses of 10 mg kg(-1) of imazalil (im) and cypermethrin (cy), and 20 mg kg(-1) of carbendazim (car) and their combinations (im, 10 mg kg(-1) + cy, 10 mg kg(-1); im, 10 mg kg(-1) + car, 20 mg kg(-1); car, 20 mg kg(-1) + cy, 10 mg kg(-1)) were applied daily for 28 days. Afterward, DNA damage in hepatocytes was evaluated by comet assay. Individually, imazalil and cypermethrin damaged DNA at alkali-labile sites, while the tail moment (TM) of carbendazim alone was similar to control but with higher tail length. In combination with carbendazim clastogen, properties of imazalils and cypermethrins were potentiated compared to all other treatments and control. There were pronounced sex differences in pattern of fragmentation between treated groups. Higher long tail nuclei (LTN) in females indicate that certain cells in females were especially prone to total nucleus disintegration. Due to synergistic effects, low environmentally present concentrations of imazalil and cypermethrin in food, and especially their mixtures with carbendazim have genotoxic potential that could be particularly dangerous over prolonged exposure in mammalian organism.
Subject(s)
Benzimidazoles/toxicity , Carbamates/toxicity , Fungicides, Industrial/toxicity , Imidazoles/toxicity , Insecticides/toxicity , Mutagens/toxicity , Pyrethrins/toxicity , Animals , Comet Assay , DNA Damage , Drug Synergism , Female , Hepatocytes/drug effects , Male , MiceABSTRACT
BACKGROUND AND OBJECTIVE: The influence of the combined application of cisplatin and sevoflurane on a variety of cell types of healthy mice or mice bearing Ehrlich ascites tumour has been investigated in an in vivo study. METHODS: The alkaline comet assay method was carried out on peripheral blood leucocytes, brain, liver, kidney and tumour cells of healthy mice or mice bearing Ehrlich ascites tumour. Groups of mice were treated intraperitoneally with cisplatin, exposed to sevoflurane or by combined treatment of sevoflurane after treatment with cisplatin for 3 consecutive days. RESULTS: The in vivo exposure to sevoflurane induced genotoxicity to all assayed cells. A strong synergistic genotoxic effect to peripheral blood leucocytes, liver and kidney cells was found in mice receiving both cisplatin and sevoflurane. In contrast, a decrease of the comet tail lengths of brain cells in the combined treatments was found as compared to cisplatin alone in both healthy (P < 0.001) and Ehrlich ascites tumour-bearing mice (P < 0.05), respectively. In addition, Ehrlich ascites tumour cells of mice treated with combined treatments showed a decrease in tail lengths (P < 0.001). These findings indicate an antagonistic effect of combined treatments. CONCLUSION: Treatment of mice with cisplatin and sevoflurane induced genotoxic effect in peripheral blood leucocytes, liver, kidney, brain and Ehrlich ascites tumour cells; synergistic effect of combined treatments was expressed in all cells but brain and Ehrlich ascites tumour cells.
Subject(s)
Anesthetics, Inhalation/toxicity , Antineoplastic Agents/toxicity , Cisplatin/toxicity , DNA Damage , DNA/drug effects , Methyl Ethers/toxicity , Animals , Brain/cytology , Brain/drug effects , Carcinoma, Ehrlich Tumor/genetics , Comet Assay/methods , Hepatocytes/drug effects , Kidney/cytology , Kidney/drug effects , Leukocytes/drug effects , Male , Mice , Sevoflurane , Statistics, NonparametricABSTRACT
The effects of the anticancer drug irinotecan combined with ethanolic extract of propolis (EEP), a water-soluble derivate of propolis (WSDP), quercetin and naringin on the growth of Ehrlich ascites tumor (EAT) and the life span of tumor-bearing Swiss albino mice were studied. Test components were given to mice intraperitoneally (i.p.) at doses of 100mg kg(-1) for three consecutive days before the i.p. injection of EAT cells (1x10(6)). Irinotecan was administered i.p. at dose of 50mg kg(-1) on days 1, 13, and 19 after tumor cell inoculation. The results clearly demonstrate the synergistic action of irinotecan and EEP on survival time. These results suggest that clinical trials using a propolis preparation EEP combined with irinotecan may be beneficial in maximizing antitumor activity and minimizing post-chemotherapeutic reactions to the cytostatic drug.
