Inihibitory effect of the ether extract of human feces on activities of mutagens: Inhibition of oleic and linoleic acids

• An ether extract of normal human faces showed inhibitory effects on the activities of several mutagens in the Ames tests. By addition of the ether extract at an amount equivalent to 0.5 g of a sample of feces, the mutagenicity of 1.5 nmole of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) on Salmonella typhimurium TA98 was completely inhibited. No killing of the bacteria was detected during this treatment. Other mutagens also subject to the inhibitio were 2-amino-6-dipyridol[1,2-a:3′,2′-d]imidazole (Glu-P-1), 2-amino-9H-pyrido[2,3-b]indole (Glob-P-2), 2-amino-3-methylimidazo[4,5-d]-quinoline (IQ), benzo[a]pyrene and aflatoxin B₁. Apart from these mutagens, which require S9 for their activation, the direct mutagen prepared from Trp-P-1 by treatment with S9 was also inhibited by the fecal extract. • The inhibitory principles in the fecal extract were fractionated by thin-layer chromatography on silica gel and were identified as oleic and linoleic acids. Whereas these unsaturated fatty acids showed stron inhibitory activities, saturated fatty acids, 1.e. stearic and palmitic acids, did not exhibit any inhibition. • Although the physiological significance of these effects of oleate and linoleate is yet to be elucidated, this finding has indicated that care must be taken in screening mutagens by the Ames tests to avoid flase negatives resulting from the presence of unsaturated fatty acids in the system. • Modulation of the activity of environmental mutagens has been extensively studies. (See reviews by De Serres, 1978; Nagao et al., 1978.) We have shown that hemin is a potent inhibitor for the activities of mutagens that bear polycyclic structures; those mutagens include Trp-P-1 (the tryptophan pyrolysis product) (Arimoto et al., 1980a), benzo[a]pyrene (Arimoto et al., 1980b) and aflatoxin B₁ (Arimoto et al., 1980b). In contrast, cysteine enhances the activity of Trp-P-1 (Negishi and Hayatsu, 1979). • We report here that ether extracts of normal human feces exhibit inhibitory actions on several mutagens in the Ames tests and that, by fractionating the extracts, we identified the inhibitory priciples as oleic and linoleic acids.