Inhibition of aminoimidazoquinoxaline-type and aminoimidazol-4-one-type mutagen formation in liquid reflux models by L-tryptophan and other selected indoles.
The essential amino acid L-tryptophan (L-Trp) was found to be an effective inhibitor of the development of mutagenicity (Ames test) in liquid-reflux models known to produce identified IQ-type mutagens, such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx), and in reflux models recently developed in our laboratory that have been found to produce novel IQ-"like" mutagens (aminoimidazol-4-ones), which we have identified as 2-amino-1-methyl-5-propylideneimidazol-4-one (TCP-1), and 2-amino-5-ethylidene-1-methylimidazol-4-one (TCP-2 or ACP). Selected indoles other than L-Trp were also found to be effective inhibitors of mutagen formation in these same reflux models. A mechanism of inhibition of mutagen formation based on the preferential reaction of mutagen precursor aldehydes with the indole-ring nitrogen of these inhibitors, rather than with creatinine, is indicated, and a new "concerted condensation model" for the formation of IQ-type mutagens proposed.
D007211:Indoles / Q000494:pharmacology*; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D011810:Quinoxalines / Q000378:metabolism; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000494:pharmacology*
D007211:Indoles; D009153:Mutagens; D011804:Quinolines; D011810:Quinoxalines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D014364:Tryptophan; C042052:2-amino-3,7,8-trimethylimidazo(4,5-f)quinoxaline; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline