Prediction of chemical carcinogenicity from molecular and electronic structures: a comparison of MINDO/3 and CNDO/2 molecular orbital methods.

Molecular orbital methods have been used to calculate the electronic structures of a number of chemical carcinogens and non-carcinogens using the MINDO/3 (Modified Intermediate Neglect of Differential Overlap, version 3) and CNDO/2 (Complete Neglect of Differential Overlap) procedures; results from the two methods show good agreement. Spatial conformations of the same series of chemicals have also been determined. High affinity for cytochromes P-448 (P450 I) and high potential for chemical carcinogenicity/toxicity show good correlation with molecular planarity (high values of area/depth2) and low values of the difference between the frontier orbital energies (delta E) of the chemical. This computer graphic procedure identifies substrates of the cytochromes P-448 and is highly suited for the rapid screening of new chemicals for potential mutagenicity, carcinogenicity and certain other forms of toxicity. The implications of these findings to the mechanism of chemical carcinogenicity are discussed.