Mutagenic activation of IQ and Me-IQ by liver and lung microsomes from rabbit and mouse, and with isolated lung cells from the rabbit.
The heterocyclic amines 2-amino-3-methylimidazo-(4,5-f)-quinoline (IQ) and 2-amino-3,4-dimethylimidazo(4,5-f)-quinoline (Me-IQ) which are formed during broiling (grilling) and cooking of protein-rich food, have previously been shown to be both carcinogenic and mutagenic. In this work IQ and Me-IQ were found to be several hundred-fold more mutagenic in liver than in lung microsomal preparations from uninduced mice and rabbits. IQ has already been found to induce tumors at about the same frequency in liver and lung in mice. Obviously, the discrepancy between the data on carcinogenicity in vivo and mutagenicity in vitro with microsomal preparations from the two organs might in part be due to the lack of detoxification mechanisms in the latter system. Freshly isolated lung cells will better mimic the in vivo situation. With the metabolically active Clara cells, IQ was much more mutagenic than Me-IQ. It has previously been shown that the Clara cells have low capacity for DNA repair. It is tempting to speculate whether the situation in the mouse is in correspondence with that described in the rabbit, in which case the cell data fits well with the in vivo carcinogenesis data.
D000818:Animals; D001711:Biotransformation; D002243:Carbolines / Q000633:toxicity; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000032:analysis; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D011817:Rabbits
D002243:Carbolines; D003580:Cytochromes; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole