TABLE 3

Correlation analysis between the extent of CYP2A immunoinhibition and the degree of NNK biotransformation, levels of CYP2A mRNA, and 7-hydroxycoumarin formation






Percentage Change in Total α-Hydroxylationa

Percentage Change in Total N-Oxidation

Percentage Change in NNAL Formation
Total α-hydroxylation (n = 29) r = 0.234b P = 0.222b
High bioactivation group r = 0.285 P = 0.268
Low bioactivation group r = 0.313 P = 0.322
Total N-oxidation (n = 29) r = 0.177 P = 0.360
High detoxification group r = 0.218 P = 0.573
Low detoxification group r = 0.156 P = 0.512
NNAL formation (n = 29) r = −0.0362 P = 0.852
CYP2A13 mRNA (n = 28) r = 0.0861 P = 0.633 r = 0.0586 P = 0.767 r = 0.112 P = 0.569
CYP2A6 mRNA (n = 24) r = −0.338 P = 0.107 r = 0.0815 P = 0.705 r = −0.0234 P = 0.960
7-Hydroxycoumarin formation (n = 27)

r = 0.0200
P = 0.920
r = 0.125
P = 0.533
r = 0.00856
P = 0.966
  • a CYP2A6/13 immunoinhibition was determined by the percentage change in NNK metabolism in the presence of a CYP2A6/13 inhibitory antibody. Immunoinhibition experiments were performed independently of other experiments that assessed NNK metabolism, mRNA expression, and coumarin 7-hydroxylation.

  • b Correlation coefficients (r) and P values were determined using Pearson's correlation analysis.