Structural basis of the genotoxicity of polycyclic aromatic hydrocarbons.

The Computer Automated Structure Evaluation (CASE) system has been applied to investigate the structural basis of the genotoxicity of 37 polycyclic aromatic hydrocarbons examined with the Escherichia coli PQ37 genotoxicity assay (SOS chromotest). CASE identified eight activating and one inactivating structural fragments responsible, for the probability and three activating and one inactivating fragment responsible for the potency of the activity (P less than or equal to 0.15). The present analysis indicate that the main activating fragments identified by CASE were similar to the descriptor for the bay (or modified bay) and K region of PAHs. Using these fragments the computer correctly predicted the probability of genotoxicity of 93.6% of the known genotoxicants and nongenotoxicants in the database. Moreover, the concordance between prediction and experimental results for molecules not in the learning set is greater than 78%.