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Cytosolic free calcium levels in isolated rat hepatocytes exposed to radical inducing xenobiotics
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Book of Abstmcts - EUROTOX 94
Safety Assessmentof lkansgenlcTomatoFruit Expressingthe TkuncateciGene cryM(b) of BacMusalias subap. bier 1715 ti.Wbl. Notebom ’ . ME. Bienenmann-Ploum t, GM. Alink *, L. Zolla 3, H.A. Kuiper‘. ’ Dept RiskAssessmentand Toxicolog RtHLT-DLO.PO. &x230.6700 AE Wageningen; * Dept. Toxicatom Agricuihrmt University Wageningen, 6700 EA mgeningen. The Netherlands: 3 Dept. Environmental Sciences. University La Tuscia, Viterbo. Ita& Transgenic tomatoes have been produced which contain chimaeric genes coding for the Insecticidal Crystal Protein Cry@(b)of &aci/&s ~uft~ien~~ and the enzyme neomycin phosphotransferase II (NPTII). To assess the food safety of CrylA(b),the same coding sequence used for plant tran~o~ation was introduced in Esche~~hia coti to provide starting material for toxicity testing. Acute effects on the digestive mucosa were tested in rats with an iliac fist&a exposed to CrylA(b) at a single dose of 2.0 mg/kg bw. Results indicated no toxicity and an extensive digestion. Thirty-day oral toxicity studies in female mice dosed up to 0.46 mg CrylA(b)/kgbwlday and male rabbits dosed 0.06 mg CrylA(b)/kgbwtday via drinkingwater did not show any deleterious effects. No anti-CrylA(b)-I, was measured in the serum of treated animals, nor total lgG concentrations were elevated compared to controls. CrylA(b)degraded rapidly under simulated digestive conditions. In vivo and in v&o no binding of Cam was observed to the brush border membrane of rodent. primate and human gut epithelial cellos.No hemolytic effects of CryiA(b)on RBC’s or functional alterations in the mucosa of isolated rat gut segments were found. Results of a 90 days feeoing trial with transgenic tomatoes in rats will be presented. Key w~fds.’ transgenic plants; food; bacterial toxin; insect resistance; feeding study
Examinationof EmbryotoxicityEffectof a TFIISISTONContraceptivePreparation G. Nowaczvk-Dura. P Czekaj. A. Plewka, V. Ciszkowa. It Department of Histology and Embryotom SitesianMedical Academy. Katowice, Poland The purpose of this review was to estimate the influence of therapeutical doses preparation TRISISTON on foetuses of experimental animals. TRISISTON contains: 6 pills - 0.03 mg of eth~~oestradiol (EE) and 0.05 mg of levonorgestrel (LE); 6 pills - 0.04 mg EE and 0.75 mg LE; 9 pills - 0.03 mg EE and 0.125 mg LE. The experim%t was performed on 100 sexually mature female rats of Wistar strain. All experimental animals were given TRISISTDN during organogenesis. Pregnancy has been solved by caesarian section in all groups, and hysterectomy was done. Number of alive and dead foetuses and number of resorptions has been determined. Results of measurements of foetuses and placentas mass. and lengths of foetuses in examined and control groups were statisticallyinsignificant.We did not find any differences in organs in histological examinations of the whole foetuses of ex~~mental rats stained according to the Wilson’s method. No congenital maiformations were noted. Statistically insigni6cant increase of the number of skeleton ossification points in foetuses of experimental groups was found, in comparison with the controls. Contraceptive preparationTRISISTON based on experimental rp ?archcomplies with all requirements of contemporary contraceptive device. Key words: oral contraception; Trisiston;embryotoxicity; rats
CytosolicFree CalciumLevels in Isolated Rat HepatocytesExposedto Radical Inducing Xenobiotica MC. Niimberger, S. Klee. FR. Unaemach. tnstituteof Pharmacology, Pharmacyand Toxicc’ogfiFacuttyof Bterinaty Medicinez Universityof Leipzig Sustained increases of hepat~ellular [Ca2+] are supposed to be an important pathobiochemical mechanism in cytotoxicity caused by foreign compounds. To check this hypothesisthe cytotoxicity of allylalcohol(3 mmol/o, bromotrichloromethane (1.5 mmoVl), cumenehydroperoxide (250 #molil) and nitrofurantoin(1 mmolfl) was related to changes of the cytosolic calcium content. Only cumenehydroperoxide and bromotrichloromethane induced a sustained calcium rise. By enhancing or reducing cytotoxicity with either BCNU (a GSH-redu~tase-inhibitory.dithiothreitol and deferoxamine, resp. the calcium rise could be further dissociated from the development of lethal cell injury. Therefore an interrelationshipbetween cytotoxicityand cytosolic calcium content was not evident. This study was supported by the Deutsche Forschungsgemeinschaft Key words: hepatotoxicity; cytosolic calcium; free radicals
Book of Abstmcts - EUROTOX 94
Safety Assessmentof lkansgenlcTomatoFruit Expressingthe TkuncateciGene cryM(b) of BacMusalias subap. bier 1715 ti.Wbl. Notebom ’ . ME. Bienenmann-Ploum t, GM. Alink *, L. Zolla 3, H.A. Kuiper‘. ’ Dept RiskAssessmentand Toxicolog RtHLT-DLO.PO. &x230.6700 AE Wageningen; * Dept. Toxicatom Agricuihrmt University Wageningen, 6700 EA mgeningen. The Netherlands: 3 Dept. Environmental Sciences. University La Tuscia, Viterbo. Ita& Transgenic tomatoes have been produced which contain chimaeric genes coding for the Insecticidal Crystal Protein Cry@(b)of &aci/&s ~uft~ien~~ and the enzyme neomycin phosphotransferase II (NPTII). To assess the food safety of CrylA(b),the same coding sequence used for plant tran~o~ation was introduced in Esche~~hia coti to provide starting material for toxicity testing. Acute effects on the digestive mucosa were tested in rats with an iliac fist&a exposed to CrylA(b) at a single dose of 2.0 mg/kg bw. Results indicated no toxicity and an extensive digestion. Thirty-day oral toxicity studies in female mice dosed up to 0.46 mg CrylA(b)/kgbwlday and male rabbits dosed 0.06 mg CrylA(b)/kgbwtday via drinkingwater did not show any deleterious effects. No anti-CrylA(b)-I, was measured in the serum of treated animals, nor total lgG concentrations were elevated compared to controls. CrylA(b)degraded rapidly under simulated digestive conditions. In vivo and in v&o no binding of Cam was observed to the brush border membrane of rodent. primate and human gut epithelial cellos.No hemolytic effects of CryiA(b)on RBC’s or functional alterations in the mucosa of isolated rat gut segments were found. Results of a 90 days feeoing trial with transgenic tomatoes in rats will be presented. Key w~fds.’ transgenic plants; food; bacterial toxin; insect resistance; feeding study
Examinationof EmbryotoxicityEffectof a TFIISISTONContraceptivePreparation G. Nowaczvk-Dura. P Czekaj. A. Plewka, V. Ciszkowa. It Department of Histology and Embryotom SitesianMedical Academy. Katowice, Poland The purpose of this review was to estimate the influence of therapeutical doses preparation TRISISTON on foetuses of experimental animals. TRISISTON contains: 6 pills - 0.03 mg of eth~~oestradiol (EE) and 0.05 mg of levonorgestrel (LE); 6 pills - 0.04 mg EE and 0.75 mg LE; 9 pills - 0.03 mg EE and 0.125 mg LE. The experim%t was performed on 100 sexually mature female rats of Wistar strain. All experimental animals were given TRISISTDN during organogenesis. Pregnancy has been solved by caesarian section in all groups, and hysterectomy was done. Number of alive and dead foetuses and number of resorptions has been determined. Results of measurements of foetuses and placentas mass. and lengths of foetuses in examined and control groups were statisticallyinsignificant.We did not find any differences in organs in histological examinations of the whole foetuses of ex~~mental rats stained according to the Wilson’s method. No congenital maiformations were noted. Statistically insigni6cant increase of the number of skeleton ossification points in foetuses of experimental groups was found, in comparison with the controls. Contraceptive preparationTRISISTON based on experimental rp ?archcomplies with all requirements of contemporary contraceptive device. Key words: oral contraception; Trisiston;embryotoxicity; rats
CytosolicFree CalciumLevels in Isolated Rat HepatocytesExposedto Radical Inducing Xenobiotica MC. Niimberger, S. Klee. FR. Unaemach. tnstituteof Pharmacology, Pharmacyand Toxicc’ogfiFacuttyof Bterinaty Medicinez Universityof Leipzig Sustained increases of hepat~ellular [Ca2+] are supposed to be an important pathobiochemical mechanism in cytotoxicity caused by foreign compounds. To check this hypothesisthe cytotoxicity of allylalcohol(3 mmol/o, bromotrichloromethane (1.5 mmoVl), cumenehydroperoxide (250 #molil) and nitrofurantoin(1 mmolfl) was related to changes of the cytosolic calcium content. Only cumenehydroperoxide and bromotrichloromethane induced a sustained calcium rise. By enhancing or reducing cytotoxicity with either BCNU (a GSH-redu~tase-inhibitory.dithiothreitol and deferoxamine, resp. the calcium rise could be further dissociated from the development of lethal cell injury. Therefore an interrelationshipbetween cytotoxicityand cytosolic calcium content was not evident. This study was supported by the Deutsche Forschungsgemeinschaft Key words: hepatotoxicity; cytosolic calcium; free radicals