Bifunctional nitrofluorenes: structure-activity relationships in Salmonella typhimurium

Abstract

Bifunctional derivatives of fluorene have long been the subject of intense study for their carcinogenic activity in animal systems (reviewed by Arcos and Argus, 1974). In vivo studies typically used the amine derivatives of fluorene and relied on the endogenous metabolic pathways of the test system to activate the chemical to its ultimate carcinogenic form. It is now possible to use shortterm bioassays, e.g. the Ames test (Ames et al., 1975), to investigate the mutagenic activity of many of the fluorene derivatives. Since Salmonella are quite sensitive to many nitroaromatics, it is also possible to study the nitro analogues of the carcinogenic and noncarcinogenic fluorene compounds. The commonality between a nitroand amino-aromatic is that the proximate mutagenic/ carcinogenic form for both is most probably the hydroxylamine derivative. A particular advantage in using the Ames Salmonella is the availability of nitroreductase-deficient strains, developed by H.S. Rosenkranz and his colleagues (Rosenkranz and Speck, 1976), that are otherwise isogenic with the standard tester strains. By combining a microsomal enzyme activating system ($9) with the TA98NR assay, one can test the effect of a nitro group on an aminofluorene and, conversely, the effect of an amino group on a nitrofluorene in TA98 without $9. This principle can be extended to testing the effect of other functional groups