- Email: [email protected]
Endocrine manipulations may increase hydroxiurea toxicity
152 STUDIES OR THE ROLE OF LIPID PEROXI~TI~ ETHANE FORFWTIONIN RATS IINVIVO
IN THE TOXICITY OF QUARTZ fSiO2) AS MEASUREDBY
ii.Kappus and H. Muliawan Sectionon Pharmacology,Med. Instituteof EnvironmentalHygiene,Universityof Dusseldorf, Gurlittstr.53. D-4000 DUsseldorf 1. West-Germany During phagocytositof quartz crystals in vivo an increase in oxygen radical formationhas been demonstrated.Because oxygen radicalsare able to induce lipid peroxidation,it has been assuwed that silicosisoccurring in man after long-terminhalationof SiO2 is due to the peroxidativebreakdownof membrane lipids of the lung. We tested this hypothesisin rats in vivo which ware treatedn5th quartz suspendedin saline by a single intraperitonealinjection.This treatmenthas been shown to result within a few weeks in lung injury which rese&les silicosis in man. Immediatelyafter the injectionof SiO2 and 1. 2, 3, 4 and 5 weeks later the expirationof ethane of the rats was followed for at least 7 h. Meanwhile the animals were kept under normal conditions.The ethane measurementwas taken, because it is the best indicatoravailableto determinelipid peroxidationin viva. The ethant expirationof the rats which had received 660 mg SiD2 per kg body weight was not increasediesaediately after treatmentwhen compared to the correspondingcontrols.Rather a slight decreasewas observed.Also after 1. 2, 3, 4 and 5 weeks there was no significant differencein ethane expirationbetween control and treated rats, alth~gh the animals treated with quartz showed lower weight gains. The animals also developedlung injury. Dur resultsdRnonstratethat a relationshipbetween lipid peroxidationand the presenceof quartz in the body does not exist. Therefore,it is likely that phagocytosis is not necessarilyassociatedwith increasedlipid peroxidation.The data also suggest that lipid peroxidationis probably not involvedin quartz toxicity.
ERMlCRINE ryulIWLATIONSIUY INCREASEHYDROXIUREATOXICITY
PREZIOSIP. and VACCA M.
DEPARmRT OF PRARMACDLDGY,CATHOLIC UNIVERSITYSCWODL OF MEDICINE L.GO F. VITO 1, 00168 RUE, ITALY. In a set of researches aimed at investigatingpossible changes in toxicity of anticancer drugs after endocrine manipulationsin the adult ;b rat (190-265 9) we found that a 6-day oral treatment with hydroxyurea (HI at doses per Kg correspondingto (80 ~/Kg/d~ and 10 times higher than (800 mg/Kg/dI the human therapeuticdose accordingto a recent treatmentschedule (3OD mg& orallyx5d),apparently toleratedin intact ratsin lethality;significant(P
IN THE TOXICITY OF QUARTZ fSiO2) AS MEASUREDBY
ii.Kappus and H. Muliawan Sectionon Pharmacology,Med. Instituteof EnvironmentalHygiene,Universityof Dusseldorf, Gurlittstr.53. D-4000 DUsseldorf 1. West-Germany During phagocytositof quartz crystals in vivo an increase in oxygen radical formationhas been demonstrated.Because oxygen radicalsare able to induce lipid peroxidation,it has been assuwed that silicosisoccurring in man after long-terminhalationof SiO2 is due to the peroxidativebreakdownof membrane lipids of the lung. We tested this hypothesisin rats in vivo which ware treatedn5th quartz suspendedin saline by a single intraperitonealinjection.This treatmenthas been shown to result within a few weeks in lung injury which rese&les silicosis in man. Immediatelyafter the injectionof SiO2 and 1. 2, 3, 4 and 5 weeks later the expirationof ethane of the rats was followed for at least 7 h. Meanwhile the animals were kept under normal conditions.The ethane measurementwas taken, because it is the best indicatoravailableto determinelipid peroxidationin viva. The ethant expirationof the rats which had received 660 mg SiD2 per kg body weight was not increasediesaediately after treatmentwhen compared to the correspondingcontrols.Rather a slight decreasewas observed.Also after 1. 2, 3, 4 and 5 weeks there was no significant differencein ethane expirationbetween control and treated rats, alth~gh the animals treated with quartz showed lower weight gains. The animals also developedlung injury. Dur resultsdRnonstratethat a relationshipbetween lipid peroxidationand the presenceof quartz in the body does not exist. Therefore,it is likely that phagocytosis is not necessarilyassociatedwith increasedlipid peroxidation.The data also suggest that lipid peroxidationis probably not involvedin quartz toxicity.
ERMlCRINE ryulIWLATIONSIUY INCREASEHYDROXIUREATOXICITY
PREZIOSIP. and VACCA M.
DEPARmRT OF PRARMACDLDGY,CATHOLIC UNIVERSITYSCWODL OF MEDICINE L.GO F. VITO 1, 00168 RUE, ITALY. In a set of researches aimed at investigatingpossible changes in toxicity of anticancer drugs after endocrine manipulationsin the adult ;b rat (190-265 9) we found that a 6-day oral treatment with hydroxyurea (HI at doses per Kg correspondingto (80 ~/Kg/d~ and 10 times higher than (800 mg/Kg/dI the human therapeuticdose accordingto a recent treatmentschedule (3OD mg& orallyx5d),apparently toleratedin intact ratsin lethality;significant(P