By using the shuttle vector pZ189 mutagenesis system, the present study provides the first direct evidence indicating that, as compared with CYP2A6, CYP2A13 is more effective in potentiation of the NNK -induced mutagenesis in human lung cells (Fig. 2), possibly, via metabolic activation of NNK (Table 1 and Fig. 4C) and formation of NNK-related DNA adducts (Figs. 4D and E).