in control hk293 cells and those expressing ugt1a4 and ugt2b7 up to a protein concentration of 2 mg ml on the other hand there was measurable sn 38g formation in cells expressing ugt1a1 which increased with increasing protein concentrations the high correlation between sn 38 and bilirubin glucuronidation suggests that ugt1a1 is the isoform involved in sn 38 glucuronidation in an effort to demonstrate that ugt1a1 also plays a role in glucuronidation of other toxic compounds the correlation between rates of formation of tas 103g sn 38g and glucuronidation of bilirubin was investigated microsomes protein 2 mg ml were obtained from liver samples from different species human rat mice and ferrets microsomes were incubated with tas 103 80 u03bcm mgcl 2 10 mm and udpga 2 mm in 0 1 m tris hcl buffer ph 7 4 for 20 minutes at 37 u00b0 c retention times of about 6 9 and 15 minutes were obtained for tas 103g tas 103 and tas 1 018 internal standard respectively after hplc separation and uv 460 nm detection there were extensive inter subject differences in the rates of tas 103 glucuronidation mean area ratio of tas 103g tas 1 018 peaks 11 2 u00b1 5 9 sd range 1 02 to 27 26 in normal liver microsomes n 18 tas 103 glucuronidation rates correlated significantly with the glucuronidation of sn 38 the active metabolite of irinotecan pearson r 0 94 p lt 0 01 and bilirubin r 0 82 p lt 0 01 suggesting the involvement ofugt1a1 and or ugt1a4 isoforms the role of ugt1a1 was confirmed using microsomes from lymphoblast cells that were specifically transfected with cdna expressing ugt1a1 ugt1a4 and ugt1a6 isoforms tas 103g formation was observed only in microsomes containing ugt1a1 enzymes mean area ratio 7.