title: 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.
abstract: 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.
authors.affiliation: Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
authors.forename: A
authors.initials: A
authors.lastname: Umemoto
authors.forename: S
authors.initials: S
authors.lastname: Grivas
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Sugimura
mesh_terms: 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
chemical_list: 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