Genotoxic effects of hyperthermia, cytostatic cisplatin and propolis on normal and tumour cells in mice

Novi pristup u liječenju tumora temelji se na primjeni kemoimunoterapije i hipertermije. Takav način liječenja može prouzročiti visoku protutumorsku učinkovitost na stanice tumora te nisku toksičnost na zdrave stanice i cjelokupni organizam nositelja tumora. Cilj ovog istraživanja bio je istražiti genotoksični i citotoksični učinak citostatika cisplatine i propolisa sa i bez primjene hipertermije na miševe nositelje Ehrlichova ascitescnog tumora (EAT-a) metodom alkalnog komet testa. Tumor smo prouzročili injiciranjem 2 x 106 tumorskih stanica u trbušnu šupljinu miševima soja Swiss albino. U preventivnoj obradi, miševima smo sedam i tri dana prije unosa tumorskih stanica i.p. injicirali pripravak vodene otopine propolisa (50 mg kg-1). Kemoterapiju (37°C) i hipertermičku kemoterapiju (43°C) s citostatikom cisplatinom (5 ili 10 mg kg-1) primijenili smo 3. dan nakon injiciranja tumorskih stanica u peritonealnu šupljinu. Rezultati alkalnog komet testa ukazuju na sinergistički učinak hipertermije, citostatika cisplatine te imunoterapije s propolisom u povećanoj zaštiti molekula DNA u leukocitima te stanicama jetre i bubrega od oštećenja uzrokovanih toksičnim učincima cisplatine. Imunomodulacija te smanjena toksičnost citostatika cisplatine s propolisom vjerojatno je mogući mehanizam protutumorske učinkovitosti. Analizom rezultata zaključili smo da propolis i njegove flavonoidne sastavnice združeni s kemoterapeuticima mogu povećati protutumorski učinak kemoterapeutika, što sugerira moguću kliničku uporabu u cilju povećanja imunosti organizma te smanjenja štetnih učinaka kemoterapeutika na normalne stanice i tkiva.A new approach to cancer treatment is based on the application chemoimmunotherapy and hyperthermia. This approach may cause a high anticancer efficiency on tumor cells and low toxicity to the healthy immune cells in the body and the holder of the tumor. The aim of this study was to explore citotoxic and genotoxic effects of citostatic cisplatin and propolis with and without hyperthermia in mice bearing Ehrlich ascites tumor (EAT) using the method of alkaline comet assay. Tumors were caused by injection of 2 x 106 tumor cells into the abdominal cavity of Swiss albino mice. Seven and three days before implantation of EAT cells the mice were injected with water solution of propolis (50 mg kg-1) into the abdominal cavity. Chemotherapy (37°C) and hypothermic chemotherapy (43°C) with cisplatin (5 or 10 mg kg-1) were given on the 3rd day after the tumor cell injection into the abdominal cavity of mice. These results of alkaline comet assay suggest the synergistic effect of hyperthermia, citostatic cisplatin and immunotherapy with propolis in increased DNA protection of leukocytes, liver and kidney cells from damages caused by toxic effects of cispaltin. It is likely that immunomodulation of propolis and reducing toxicity of chemotherapy treatment with propolis may be possible mechanism of antitumor efficiency. The analysis of the results has led us to the conclusion that the combination of water solution of propolis with chemotherapeutics could increase the antitumor potential of chemotherapeutic agents which suggests the benefits of potential clinical use in order to maximize immunity of organism and minimize harmful effects of chemotherapeutic agents on normal cells and tissues