In vitro reaction of hydroxyamino derivatives of MeIQx, Glu-P-1 and Trp-P-1 with DNA: 32P-postlabelling analysis of DNA adducts formed in vivo by the parent amines and in vitro by their hydroxyamino derivatives.
The synthetic hydroxyamino derivatives of three mutagenic and carcinogenic heterocyclic amines present in cooked foods and amino acid pyrolysates, 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), were reacted with DNA in vitro. Their reactivities were increased by addition of 10-fold excess of acetic anhydride. 32P-Postlabelling analysis of the adducts formed in these in vitro reactions revealed that almost all the adducts of the hydroxyamino derivatives of MeIQx and Glu-P-1 were the same as those formed in liver DNA of rats intragastrically treated with the parent amines. In contrast, analysis of Trp-P-1--DNA adducts showed that the adducts formed in vitro were minor components of those formed in vivo; the two main adducts formed in vivo were not formed in vitro. Thus, MeIQx and Glu-P-1 may be metabolized in vivo to hydroxyamino derivatives and/or their esterified forms, such as N-acetoxy derivatives that form DNA adducts. Formation of adducts by Trp-P-1, however, may occur through more complicated metabolic pathways. Elucidation of the structures of DNA adducts in vivo is necessary to clarify this problem.
Yamashita
K
K
Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
Umemoto
A
A
Grivas
S
S
Kato
S
S
Sugimura
T
T
D000818:Animals; D001665:Binding Sites; D002243:Carbolines / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D006898:Hydroxylamines / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D011810:Quinoxalines / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D002243:Carbolines; D002273:Carcinogens; D006898:Hydroxylamines; D007093:Imidazoles; D009153:Mutagens; D011810:Quinoxalines; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D004247:DNA; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole