Inhibition of NNK α-hydroxylation by inhibitory antibodies
HLM Sample | Rates of α-Hydroxylationa | Percentage Inhibition of Total α-Hydroxylation by P450 2A6- and P450 2B6-Selective Antibodiesb | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Methylc | Methylened | Total | 2A6 | 2B6 | 2A6 and 2B6 | |||||
| pmol/min/mg | ||||||||||
| 1 | 18.1 ± 2.3 | 4.8 ± 0.7 | 22.9 ± 2.9 | 50 | 16 | 67 | ||||
| 2 | 21.5 ± 1.9 | 8.2 ± 0.4 | 29.7 ± 2.2 | 53 | 17 | 71 | ||||
| 39 | 6.4 ± 0.6 | 1.1 ± 0.4 | 7.5 ± 0.9 | 46 | 39 | 60 | ||||
| 129 | 4.8 ± 1.5 | 2.4 ± 1.2 | 7.2 ± 2.7 | 44 | 0 | 47 | ||||
| 130 | 17.9 ± 2.3 | 0.5 ± 0.2 | 18.4 ± 2.5 | 50 | 4 | 59 | ||||
| 131 | 28.7 ± 16.4 | 8.8 ± 6.2 | 37.5 ± 22.6 | 64 | 11 | 66 | ||||
| 132 | 18.4 ± 5.7 | 0.3 ± 0.4 | 18.7 ± 5.4 | 18 | 15 | 30 | ||||
| 133 | 6.8 ± 0.6 | 1.4 ± 0.3 | 8.2 ± 0.8 | 69 | 16 | 66 | ||||
| 134 | 13.8 ± 1.4 | 2.8 ± 0.4 | 16.7 ± 1.7 | 42 | 21 | 63 | ||||
| 141 | 27.5 ± 5.2 | 8.8 ± 3.2 | 36.3 ± 8.3 | 42 | 0 | 49 | ||||
↵ a HLMs (0.3 mg) were incubated with [3H]NNK (80 μM; specific activity, 0.4 μCi/nmol) for 30 min. Values are mean rates, n = 4 (except HLM 1, n = 2 and HLMs 133 and 2, n = 3).
↵ b Percentage inhibition calculated from duplicate reactions in the presence and absence of inhibitory antibodies.
↵ c HPB formation.
↵ d OPB and OPBA formation.