Metabolic Activation of 2-Aminofluorene in the Salmonella Mutagenicity Assay by Different S-9 Preparations

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Abstract
Before exerting a carcinogenic or mutagenic effect, many chemicals must undergo metabolic activation. The most widely used activation system is the 9,000 g supernatant fraction (S-9) of rat liver homogenate, prepared from male rats pretreated with Aroclor 1254 (AC). The present study compares the capabilities to induce metabolic activation of 2-aminofluorene (2-AF), using different sources of S-9 preparations as a test-promutagen, both in the Ames test and in the minimal saline liquid medium (MSLM). In particular, S-9 preparations of liver and kidney fractions from male rats and guinea pigs, with or without AC or phenobarbital (PB) pretreatment, were used. The 2-AF was tested in Salmonella typhimurium TA 1538 strain (frame-shift mutation) at different level of concentrations. In the Ames test the enzymatic activation of liver fractions, induced by PB, shows a large increase of mutagenicity of 2-AF in both animal species studied. The AC pretreatment in rats significantly reduced the mutagenic activity of 2-AF, when compared with controls. With rat renal microsomes no differences were observed in mutagenicity as compared with controls. A significant increase was seen in the microsomes of guinea pigs pretreated with AC. The experiments carried out with MSLM confirmed the results in full. Abbreviations. 2-AF, 2-aminofluorene; 2-AAF, 2-acetylaminofluorene; PB, sodium phenobarbital; AC, Aroclor 1254; C, uninduced control; MSLM, minimal saline liquid medium