CYP-dependent catalytic activities, amounts of ellipticine metabolites and DNA adducts formed by ellipticine in human hepatic microsomes
| Human hepatic microsomal samples . | pmol CYP per mg protein . | EROD (CYP1A1/2) * . | Coumarin 7-hydroxylation (CYP2A6) * . | Tolbutamide methyl hydroxylation (CYP2C9) * . | Bufuralol 1′-hydroxylation (CYP2D6) * . | Chlorzoxazone 6-hydroxylation (CYP2E1) * . | Testosterone 6β-hydroxylation (CYP3A4) * . |
|---|---|---|---|---|---|---|---|
| H1 | 80 | 5.65 | 0.93 | 0.76 | 2.46 | 1.80 | 8.44 |
| H2 | 90 | 4.09 | 1.42 | 0.06 | 0.34 | 0.69 | 2.22 |
| H3 | 270 | 6.34 | 2.03 | 0.18 | 5.55 | 2.09 | 6.31 |
| H4 | 60 | 7.19 | 0.40 | 0.06 | 3.71 | 1.83 | 14.39 |
| H5 | 220 | 10.82 | 0.84 | 0.17 | 2.53 | 2.45 | 10.19 |
| H6 | 140 | 11.73 | 0.98 | 0.26 | 0.92 | 2.61 | 6.94 |
| H7 | 460 | 6.86 | 0.43 | 0.11 | 4.11 | 1.37 | 3.96 |
| H8 | 400 | 12.08 | 0.58 | 0.15 | 3.13 | 1.51 | 6.86 |
| Average value § | 215 (141.8) | 8.095 (2.83) | 0.95 (0.51) | 0.219 (0.214) | 2.84 (1.58) | 1.79 (0.577) | 7.41 (3.50) |
| Human hepatic microsomal samples . | pmol CYP per mg protein . | EROD (CYP1A1/2) * . | Coumarin 7-hydroxylation (CYP2A6) * . | Tolbutamide methyl hydroxylation (CYP2C9) * . | Bufuralol 1′-hydroxylation (CYP2D6) * . | Chlorzoxazone 6-hydroxylation (CYP2E1) * . | Testosterone 6β-hydroxylation (CYP3A4) * . |
|---|---|---|---|---|---|---|---|
| H1 | 80 | 5.65 | 0.93 | 0.76 | 2.46 | 1.80 | 8.44 |
| H2 | 90 | 4.09 | 1.42 | 0.06 | 0.34 | 0.69 | 2.22 |
| H3 | 270 | 6.34 | 2.03 | 0.18 | 5.55 | 2.09 | 6.31 |
| H4 | 60 | 7.19 | 0.40 | 0.06 | 3.71 | 1.83 | 14.39 |
| H5 | 220 | 10.82 | 0.84 | 0.17 | 2.53 | 2.45 | 10.19 |
| H6 | 140 | 11.73 | 0.98 | 0.26 | 0.92 | 2.61 | 6.94 |
| H7 | 460 | 6.86 | 0.43 | 0.11 | 4.11 | 1.37 | 3.96 |
| H8 | 400 | 12.08 | 0.58 | 0.15 | 3.13 | 1.51 | 6.86 |
| Average value § | 215 (141.8) | 8.095 (2.83) | 0.95 (0.51) | 0.219 (0.214) | 2.84 (1.58) | 1.79 (0.577) | 7.41 (3.50) |
NOTE. All results are presented as means of duplicate experiments. Assays for CYP activities were carried out as described previously (11).
Abbreviations: EROD, 7-ethoxyresorufin O-deethylation; n.d., not detectable (<0.001 pmol ellipticine metabolites/min/nmol CYP).
CYP activities in nmol/min/nmol CYP, except for EROD activity, which is in pmol/min/nmol CYP.
The pmol ellipticine metabolites/min/nmol CYP.
Relative adduct labeling (RAL)/107nucleotides per nmol CYP.
Arithmetic means for eight hepatic microsomal samples (H1-H8), values in parentheses are SDs, representing the interindividual variability.