In order to better understand the mechanisms leading to DNA modification, we undertook a study on human cell lines representative of target organs (lungs and bladder). We have shown that the formation of covalent adducts is the major deleterious pathway. More interestingly, we observed that adduct formation in lung cells was greater at low than at high concentration of benzo[a]pyrene (B[a]P), which is the most toxic PAH. In addition, we observed that a mixture of B[a]P with other PAHs leads to a decrease in the level of adducts compared to pure B[a]P. This unexpected result is explained by the metabolizing properties of lung cells, which require a certain threshold of PAH to ensure full induction of protective proteins. These observations illustrate the difficulty of predicting the toxicity of the mixture of compounds. The general approach using "toxic equivalence factors" is based on additive effects, but does not take into account the potentiation of inhibitory effects observed with PAHs. More sophisticated models requiring more experimental data are needed.