TABLE 1

Effects of chemical inhibitors on 5′-DFCR, 5′-DFUR, and 5-FU formation in the combination of human liver microsomes and cytosol Capecitabine (100 μM) was incubated with the combination of microsomes (0.5 mg/ml) and cytosol (2.5 mg/ml) obtained from BD Gentest in the presence or absence of chemical inhibitors. BNPP, DFP, THU, and TPI concentrations ranged from 0.1 to 10 μM, 0.01 to 1 μM, 0.04 to 4 μM, and 5 to 100 nM, respectively. Each data represents the mean of duplicate determinations. Values in parentheses indicate the percentages of the control activities.


Inhibitor



5′-DFCR Formation

5′-DFUR Formation

5-FU Formation
μM pmol/min/mg protein
None 2.9 (100) 7.4 (100) 4.8 (100)
BNPP 1 1.1 (37) 3.9 (52) 3.0 (63)
2 0.8 (28) 4.1 (55) 2.4 (50)
10 0.2 (4) 1.7 (23) 1.6 (33)
DFP 0.1 1.9 (65) 5.4 (72) 3.6 (74)
0.2 1.1 (38) 3.3 (45) 2.5 (52)
1 0.1 (5) 0.0 (0) 1.3 (28)
THU 0.04 2.9 (100) 4.3 (58) 3.7 (78)
0.1 3.0 (104) 2.0 (27) 2.9 (61)
1 3.7 (129) 0.0 (0) 1.2 (24)
TPI 0.01 3.3 (112) 9.6 (129) 2.3 (47)
0.02 3.3 (114) 11.3 (153) 0.6 (12)

0.1
3.7 (127)
11.4 (153)
0.0 (0)