(2) Both CYP2A6 and CYP2A13 significantly enhance the α-hydroxylation metabolism of NNK; and the α-hydroxylation activity of CYP2A13 is markedly higher than that of CYP2A6. (3) Distribution patterns of NNK metabolites (NNAL vs. the other four secondary metabolites) in our cellular model are consistent with the previous studies using human tissue explants.