The modulatory effects of tryptamine and tyramine on the S9-mediated mutagenesis of IQ and MeIQ in Salmonella strain TA98.
The S9-mediated mutagenesis of IQ and MeIQ in Salmonella strain TA98 was modulated by introduction to the assay of tryptamine or tyramine. Both biogenic amines inhibited or enhanced the mutagenic response as a function of amine concentration, strain of rat used as the S9 source, and the IQ-type mutagen tested. Enhancement of IQ mutagenesis by tryptamine (10-80 microM) was observed in the presence of S9 preparations derived from Aroclor 1254-pretreated Fischer rats; the enhancing effect ceased at tryptamine concentrations > 160 microM. When Sprague-Dawley-S9 or Wistar-S9 were used for activation, the enhancement of IQ mutagenesis by tryptamine shifted to inhibition at tryptamine concentrations > 40 microM, with Sprague-Dawley-S9, and > 20 microM, with Wistar-S9. By contrast, MeIQ-mutagenesis was enhanced by tryptamine (10-160 microM), regardless of the rat strain used as S9 source. Tyramine was a weaker enhancer of MeIQ mutagenesis than was tryptamine and, unlike tryptamine, its inhibitory effects on IQ mutagenesis were observed only with Wistar-S9. Tryptamine (10-80 microM) inhibited cytochromes P450IA1 and P450IA2 activities, monitored by the O-deethylation of ethoxyresorufin and Glu-P-1 mutagenesis in TA98, respectively. These data suggest that the effects of biogenic amines on IQ and MeIQ bioactivation are complex. Furthermore, this study demonstrates that tryptamine and tyramine act both as enhancers (comutagens) and as inhibitors (antimutagens) of IQ and MeIQ mutagenesis, depending on the testing conditions.
Experimental Carcinogenesis and Mutagenesis Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27711.
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Abu-Shakra
D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles / Q000378:metabolism; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D010078:Oxazines / Q000378:metabolism; D011804:Quinolines / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344 / Q000378:metabolism; D017207:Rats, Sprague-Dawley / Q000378:metabolism; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity; D014363:Tryptamines / Q000008:administration & dosage*; D014439:Tyramine / Q000008:administration & dosage*
D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D010078:Oxazines; D011804:Quinolines; D014363:Tryptamines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C030820:tryptamine; C007649:ethoxyresorufin; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline; D014439:Tyramine