Rules of molecular geometry for predicting carcinogenic activity of unsubstituted polynuclear aromatic hydrocarbons

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Abstract
The rules of molecular geometry for predicting carcinogenic activity of polynuclear aromatic hydrocarbons (PAH) have been applied to a series of 50 unsubstituted PAH, and predicted carcinogenic activity is in good agreement with the results of testing for complete carcinogenic activity in mice and/or rats. The rules were developed from a knowledge of the center or centers of highest chemical or biochemical reactivity and are consistent with a unified hypothesis which states that the first step in the metabolic activation of unsubstituted PAH is the biochemical introduction of a methyl group. This bioalkylation reaction 1) takes place between certain PAH and S‐adenosyl‐L‐methionine and is catalyzed by cytosolic methyltransferase, 2) offers a means of probing for centers of reactivity in PAH, 3) provides a biochemical link between unsubstituted preprocarcinogens of aromatic type ArX and alkyl‐substituted procarcinogens of aromatic type ArCH2X (where X = H), and 4) makes it possible to include compounds of both aromatic types, in a consistent theory of aromatic hydrocarbon activation which incorporates alkyl substitution. The present study reveals that there are structural determinants of carcinogenicity.

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