Table 2

Antibody-mediated inhibition of coumarin 3,4-epoxide formation in hepatic microsomes

Anti-CYP1A1/2 IgG2-aAnti-CYP2E1 IgG2-bAnti-CYP1A1/22-aand Anti-CYP2E1 IgG2-b
% of Control
Mouse2-c 75 ± 796 ± 462 ± 2
Rat16 ± 0.534 ± 216 ± 0.8
H00172-d 623333
H00184131 8
H0019374813

Coumarin 3,4-epoxidation, measured viao-hydroxyphenylacetaldehyde production, was inhibited in liver microsomes by incubation with antibodies toward CYP1A and CYP2E forms.

  • 2-a  Rabbit anti-rat CYP1A1/2 IgG inhibits rat, mouse, and human CYP1A1 and CYP1A2 but is not reported to cross react with other CYP450 forms.

  • 2-b  Monoclonal mouse anti-human CYP2E1 IgG is selective for CYP2E1. This antibody inhibits rat, mouse, and human CYP2E1.

  • 2-c  Mouse and rat values are the mean ± S.E. of triplicate determinations. Controlo-hydroxyphenylacetaldehyde formation rates at 50 μM coumarin were 1.6 ± 0.05 and 0.37 ± 0.02 nmol/min/mg of protein in mouse and rat hepatic microsomes, respectively.

  • 2-d  Three individual human liver microsomal samples were examined (H0017, H0018, H0019). Values are the average of duplicate determinations. Control values at 500 μM coumarin were 0.51, 0.34, and 0.18 nmol ofo-hydroxyphenylacetaldehyde/min/mg in H0017, H0018, and H0019, respectively.