ISOLATED GLOMERULI OF THE ATLANTIC HAGFISH MYXINE GLUTINOSA AS AN ALTERNATIVE IN-VITRO MODEL TO STUDY GLOMERULAR PROTEIN-METABOLISM IN PHARMACOTOXICOLOGY OF ANTICANCER DRUGS

This study was designed to validate an alternative in vitro system wit h isolated glomeruli of the Atlantic hagfish Myxine glutinosa as a mod el to study alterations in glomerular protein metabolisms in pharmaco- toxicology of anticancer drugs. A morphometric characterization of the glomeruli of Myxine glutinosa reveals a calculated glomerular volume of 180 nl/glomerulus. The glomerular extracellular volume, measured as inulin space, is 38.5 nl/glomerulus. Total glomerular protein content of Myxine glutinosa amounts to 3.56 mu g/glomerulus and total DNA con tent to 0.44 mu g/glomerulus. Metabolic properties, estimated as glome rular protein synthesis, are comparable with mammalian glomeruli. The glomeruli of Myxine glutinosa are viable in a tissue culture for up to 12 hr. The incorporation rate of radiolabeled amino acids into glomer ular, acid-precipitable proteins is almost identical to that of rats ( e.g. Myxine glutinosa 1091 +/- 98 DPM/mu g DNA vs. rat 1340 +/- 84 DPM /mu g DNA after 4 hr incubation). To evaluate how nephrotoxic substanc es affect glomerular metabolism in this model the anticancer drug Adri amycin (ADR) was used to experimentally induce a glomerular lesion. AD R caused an increase in glomerular protein synthesis in isolated glome ruli of Myxine glutinosa, which is in accordance with data found in ra ts. Cisplatin, in contrast, known to mainly interfere with tubular int egrity, had no effect on glomerular protein synthesis, confirming the specificity of the model. The isolated glomeruli of Myxine glutinosa a re suggested as a valid alternative multicellular in vitro system for studying alterations in glomerular metabolism under pharmaco-toxicolog ical conditions and for the evaluation of specific target-cell toxicit y of selected nephrotoxins.