DRUG AND XENOBIOTIC GLUCURONIDATION CATALYZED BY CLONED HUMAN LIVER UDP-GLUCURONOSYLTRANSFERASES STABLY EXPRESSED IN TISSUE-CULTURE CELL-LINES

Two human UDP-Glucuronosyltransferase (UGT) cDNA clones were stably in tegrated into V79 chinese hamster fibroblast cells and the functional enzymes were expressed in this heterologous environment, More than 100 drugs and xenobiotics were used as substrates for glucuronidation, ca talysed by the cloned UGTs to determine the chemical structures accept ed as substrates. UGT HP1 exhibited a limited specificity for planar p henolic compounds, whereas UGT HP4 was more promiscuous in acceptance of non-planar phenols, anthraquinones, flavones, aliphatic alcohols, a romatic carboxylic acids, steroids and many drugs of varied structure. These conclusions are illustrated here -by using a series of alkyl- a nd halophenols. This work indicates the considerable potential value i n use of these recombinant cell lines to study human drug glucuronidat ion.