Demethylation of methoxychlor and mono-OH-M by rat and human liver microsomes
| Liver Microsomes1-a | Substrate | Incubation Time | Metabolites | |
|---|---|---|---|---|
| Mono-OH-M | Bis-OH-M | |||
| nmol/mg | ||||
| Rat | Methoxychlor (25 μM) | 10 min | 6.9 ± 0.3 | 3.5 ± 0.3 |
| Human (H056) | Methoxychlor (25 μM) | 10 min | 1.4 ± 0.1 | ND1-b |
| Human (H080) | Methoxychlor (25 μM) | 10 min | 3.2 ± 0.2 | ND |
| Human (H166) | Methoxychlor (25 μM) | 10 min | 4.3 ± 0.2 | ND |
| Human (H225) | Methoxychlor (25 μM) | 10 min | 16.1 ± 0.2 | 2.0 ± 0.1 |
| Rat | Mono-OH-M (20 μM) | 60 min1-c | 17.0 ± 0.1 | |
| Human (H056) | Mono-OH-M (20 μM) | 60 min | 2.1 ± 0.2 | |
| Human (H080) | Mono-OH-M (20 μM) | 60 min | 3.7 ± 0.1 | |
| Human (H166) | Mono-OH-M (20 μM) | 60 min | 4.8 ± 0.6 | |
| Human (H225) | Mono-OH-M (20 μM) | 60 min | 14.0 ± 1.7 | |
↵1-a Liver microsomes (1 mg/ml) from four human subjects or male rats (pooled from four animals) were incubated in the presence of methoxychlor or mono-OH-M and NADPH for 10 and 60 min, respectively, as described in “Materials and Methods.” Values represent the mean ± SEM of three determinations. For cross-referencing purposes, our sample numbers for the human liver microsomes correspond to the last three digits of the number assigned by the vendor.
↵1-b ND, not detected. Longer incubation times are necessary to detect bis-OH-M in these liver samples.
↵1-c With mono-OH-M as substrate, long incubation times of 60 min are required to detect and quantify accurately bis-OH-M formation.