Mechanistic Insights Gained from an Analysis of Carcinogenic Polycyclic Aromatic Hydrocarbons with the Computer Automated Structure Evaluation System

Abstract
The Computer Automated Structure Evaluation System (CASE) was used to identify the structural components responsible for either the mutagenicity or the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). These were found not to overlap and some of the structural components were endowed with much more biological activity than others. A study was then undertaken to determine whether these structural features could explain the mutagenicity and carcinogenicity of 7,12-dimethylbenz(a)anthracene (DMBA). It was found that the structures identified by CASE could explain the mutagenicity and carcinogenicity qualitatively as well as quantitatively. Moreover, the identified structures were entirely consistent with recent findings on the metabolism and DNA adduct formation of DMBA. These results are taken to indicate that CASE can be used to identify the structures in a molecule (e.g., PAH) that are sites of metabolism. Laboratory studies can then focus on that portion of the molecule.

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