Table 1.

Effects of various anticancer drugs on DMXAA glucuronidation and 6-methylhydroxylation by human liver microsomes¹

	Glucuronidation (% enzyme activity remaining)		6-Methylhydroxylation (% enzyme activity remaining)
Drugs	at 100 µm inhibitor	at 500 µm inhibitor	100 µm inhibitor	500 µm inhibitor
Folic acid	73 ± 8	70 ± 2	102 ± 5	111 ± 12
Vincristine	74 ± 14	46 ± 8	101 ± 0	67 ± 14
Amsacrine	82 ± 12	27 ± 1	102 ± 19	91 ± 5
Daunorubicin	84 ± 19	63 ± 7	59 ± 2	15 ± 2
Paclitaxel	88 ± 7	78 ± 5	98 ± 8	95 ± 6
Cisplatin	91 ± 5	67 ± 2	100 ± 10	86 ± 7
DACA	96 ± 1	71 ± 16	17 ± 2	6 ± 1
Irinotecan	97 ± 7	71 ± 4	95 ± 9	92 ± 5
Tirapazamine	97 ± 7	95 ± 7	93 ± 3	86 ± 4
Vinblastine	99 ± 4	40 ± 0	104 ± 9	113 ± 1
6-Thioguanine	100 ± 2	98 ± 7	89 ± 2	64 ± 1
Cyclophosphamide	101 ± 29	74 ± 12	95 ± 2	85 ± 4
6-Mercaptopurine	102 ± 5	96 ± 10	97 ± 8	94 ± 6
5-Fluorouracil	104 ± 11	103 ± 7	97 ± 7	96 ± 10
Methotrexate	108 ± 8	88 ± 2	109 ± 8	89 ± 14
Melphalan	113 ± 15	104 ± 15	99 ± 7	101 ± 5

¹For glucuronidation, DMXAA (100 µm, ≈ K_m) was incubated for 20 min at 37 °C with 0.1 mg ml⁻¹ Brij 58-activated liver microsomes from pooled HL6, HL7 and HL8 in the presence of various anticancer drugs. For 6-methylhydroxylation, DMXAA (25 µm, ≈ K_m) was incubated for 40 min at 37 °C with 1.0 mg ml⁻¹ liver microsomes from HL12, HL13 and HL14 in the presence of various anticancer drugs. Results are the mean ± s.d. of at least three determinations from pooled human liver microsomes for glucuronidation and mean ± s.d. of data from three individual livers for 6-methylhydroxylation.