| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
To explore the physiological roles of drug-metabolizing enzymes in peripheral blood cells, we examined which isoforms of cytochrome P450 (CYP) and conjugation enzymes (sulfotransferases (SULTs), UDP-glucuronyl transferases (UGT) and glutathione S-transferases (GST)) families were expressed in human myeloid leukemia cell lines (U937, HL-60 and K562) and lymphoid cell lines (BALL-1, MOLT-4 and Jurkat) by RT-PCR. We observed relatively high expression of CYP1A1, CYP1B1, CYP2A6, CYP2A7, CYP2D6, and CYP2E1 in all cell types, but CYP2A13 and CYP2C9 expression was not detected. Expressions of aryl hydrocarbon (Ah) receptor and Ah receptor nuclear translocater (ARNT), which mediate induction of the CYP1 family, were also detected in all cell types. Cell-type specific expression of CYP3A4 and CYP3A5 was observed in MOLT-4 and K562 cells. Weak, but significant, expression of CYP3A7 was detected in K562 cells. We detected expression of SULT1A1, 1A3 and 1C2 in all cell lines although cell-type specific expressions were observed for SULT1B1 (U937 and Jurkat) and SULT2A1 (K562). Expression of UGT1A family, which is known to metabolize many drugs and xenobiotics, was exclusively observed in MOLT-4 and BALL-1. BALL-1 expressed 8 sub families of UGT1A and MOLT-4 expressed 2 UGT1A sub families. All cell lines expressed GSTA4, P1 and T1, however, GSTM1 expression, which is supposed to detoxify carcinogens in cigarette smoke, was detected only in MOLT-4 cells. Oxidative stress (hydroperoxide) induced CYP3A4 and GSTP1 expressions in K562 cells. Chemical inducers (p-naphthoflavone and 3-methylcholanthren) induced CYP1A1 expression in MOLT-4 cells. The profile of drug-metablizing enzymes in the culture cells reported here provides information that furthers our understanding of the physiological roles of drug metabolizing enzymes in human blood cells.
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