Table 1.
AAI-DNA adduct formation catalyzed by human wild-type CYP1A1, 1A2 and 1B1, and their mutants CYP1A1-S122A, CYP1A2-T124V, and CYP1B1-A133S. All CYPs were reconstituted with rat POR in a ratio of 1:1 or with rat recombinant POR alone in liposomes.
| Enzymatic System | Levels of DNA Adducts in RAL a (Mean ± SD/108 Nucleotides) | |||
|---|---|---|---|---|
| dG-AAI | dA-AAI | dA-AAII | Total | |
| POR | 0.22 ± 0.05 | 0.61 ± 0.08 | 0.12 ± 0.03 | 0.95 ± 0.14 |
| CYP1A1 + POR | 0.43 ± 0.08 | 1.89 ± 0.34 | 0.17 ± 0.04 | 2.49 ± 0.38 *** |
| CYP1A1-S122A mutant + POR | 0.22 ± 0.06 | 0.71 ± 0.10 | 0.11 ± 0.05 | 1.04 ± 0.21 |
| CYP1A2 + POR | 0.89 ± 0.10 | 3.85 ± 0.48 | 0.38 ± 0.05 | 5.12 ± 0.87 *** |
| CYP1A2-T124V mutant + POR | 0.24 ± 0.05 | 0.82 ± 0.10 | 0.10 ± 0.03 | 1.16 ± 0.23 |
| CYP1B1 + POR | 0.22 ± 0.05 | 0.61 ± 0.10 | 0.10 ± 0.05 | 0.93 ± 0.18 |
| CYP1B1-A133S mutant + POR | 0.40 ± 0.08 | 1.22 ± 0.14 | 0.21 ± 0.04 | 1.83 ± 0.19 *** |
a RAL, relative adduct labelling; Comparison was carried out by Student t-test; *** p < 0.001, different from amounts of DNA adducts generated by POR alone.