Ames assay mutagenicity and electronic structure calculations of bromomethylfluoranthenes, chloromethylfluoranthenes, and hydroxymethylfluoranthenes.

ABSTRACT

The mutagenicities of the five possible isomers of bromomethylfluoranthene, chloromethylfluoranthene, and hydroxymethylfluoranthene were determined in the Ames assay using strains TA100 and TA98 without the addition of rat-liver S9 tissue extract. The mutagenicities of the bromomethyl and chloromethylfluoranthenes ranged from 25 to 6000 rev./nmol. The most mutagenic compound was 8-chloromethylfluoranthene in strain TA98 (6000 rev./nmol). The reactivities of the bromomethylfluoranthenes and the chloromethylfluoranthenes were estimated from electronic structure calculations using the MNDO and the PM3 semi-empirical methods. The bromomethylfluoranthenes showed the smallest differences between the heats of formation of the carbocations and the heats of formation of the parent bromomethyl derivatives. Therefore, the bromomethylfluoranthenes were estimated to be the most reactive of the halomethylfluoranthenes studied. The compound that showed the largest change in heat of formation (the most stable halomethylfluoranthene) going from the halomethylfluoranthene to the carbocation was 2-chloromethylfluoranthene. However, neither the most reactive nor the most stable halomethylfluoranthenes were the most mutagenic in either strain of bacteria. These results are interpreted to suggest that the reactivity of the parent halomethylfluoranthene is not a critical factor in the mechanism by which these compounds are mutagenic, but some other factor, perhaps intercalation, must be a critical step in the mechanism of mutagenesis of these compounds.