Table 2

Correlation of various CYP isoform catalytic activities with methoxychlor mono-O-demethylation in a panel of human liver microsomes

Activity2-aP450 Isoforms InvolvedAdjusted R2 Value Determined by Univariate Linear Regression
1 μM methoxychlor25 μM methoxychlor
Total P4500.190.222-150
Cytochromec reductase−0.09−0.06
EthoxycoumarinO-deethylaseMultiple−0.04−0.05
Phenacetin O-deethylaseCYP1A20.54**0.332-150
Coumarin 7-hydroxylaseCYP2A60.00−0.03
Mephenytoin 4′-hydroxylaseCYP2C190.79***0.52***
DextromethorphanO-demethylaseCYP2D6−0.070.01
Chlorzoxazone 6-hydroxylaseCYP2E1−0.09−0.07
Testosterone 6β-hydroxylaseCYP3A4−0.09−0.04
Lauric acid ω-hydroxylaseCYP4A−0.09−0.05
AdjustedR 2 value determined by multivariate linear regression
Mephenytoin 4′-hydroxylase/CYP2C19/ 0.962-b 0.652-c
Phenacetin O-deethylase/ CYP1A2/
Coumarin 7-hydroxylaseCYP2A6
  • 2-150 , indicates statistical significance, p < 0.05. **, indicates statistical significance, p < 0.01. ***, indicates statistical significance, p < 0.001.

  • 2-a Isoform-specific catalytic activities were measured by the vendor (IIAM, Exton, PA). Mono-O-demethylation of methoxychlor was measured as described in the materials and methods in 13 and 16 livers using 1 and 25 μm methoxychlor, respectively.

  • 2-b The model was significant overall, p < 0.001. CYP2C19, CYP2A6, and CYP1A2 marker activities made a significant contribution, with p values of <0.001, <0.001, and <0.05, respectively.

  • 2-c The model was significant overall, p < 0.001. CYP2C19, but not CYP2A6 or CYP1A2 marker activities made a significant contribution, with p values of <0.01, orp = 0.055 and 0.161, respectively.