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Anti-carcinogenic action of phenobarbital given simultaneously with diethylnitrosamine in the rat
Affiliation:1. Charité - Universitätsmedizin Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Institute for Theoretical Biology, Germany;2. Charité - Universitätsmedizin Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Medical Department of Hematology, Oncology, and Tumor Immunology, Molecular Cancer Research Center, Germany;3. Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy;4. Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo (FG), Italy;5. Institute for Theoretical Biology, Institut für Biologie, Humboldt-Universität zu Berlin, Germany;6. Department of Molecular Biology, Max Planck Institute for Infection Biology Berlin, Germany;7. IRCCS SDN, Naples, Italy;8. Department of General, Laparoscopic and Robotic Surgery, Azienda Ospedaliera Specialistica dei Colli, Monaldi Hospital, Via Leonardo Bianchi, 80131 Naples, Italy;1. Chemistry Department, Faculty of Science, Suez Canal University, Ismaillia 41522, Egypt;2. Faculty of Pharmacy, Suez Canal University, Ismaillia 41522, Egypt;3. Institute of Biotechnology for Post Graduate Studies and Research, Suez Canal University, Egypt
Abstract:
The present work has been planned in order to elucidate the effect of phenobarbital (PB: 15 mg per rat of ingested dose) on carcinogenesis when it is administered simultaneously with diethylnitrosamine (DEN: 10 mg/kg/day). Wistar rats (180 g) were treated by DEN alone or by DEN + PB during 2, 4 and 6 weeks according to our schedule for hepatocarcinogenesis. After the end of the treatment, the number and the size of induced PAS positive preneoplastic foci was significantly reduced when PB was given simultaneously with DEN for 4 and 6 weeks. The mitotic inhibition and the production of micronuclei normally observed after partial hepatectomy in DEN treated rats were also significantly decreased in DEN + PB treated rats. When the treatment last only 2 weeks, the presence of PB did not change significantly the last parameters. In DEN + PB treated rats, the survival was prolonged and the tumor incidence decreased as compared with the results obtained by DEN alone. It is concluded that PB, which promotes carcinogenesis when administered after the DEN treatment, reduces the carcinogen effect when given simultaneously with DEN. This ‘anti-carcinogen’ effect acts on the initiation as well as on the promotion of the precancerous lesions. Biochemical investigations are in progress to obtain more information about this ‘paradoxical’ PB effect.
Keywords:
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