In vitro reaction of hydroxyamino derivatives of MelQx, 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
- 1 January 1988
- journal article
- research article
- Published by Oxford University Press (OUP) in Mutagenesis
- Vol. 3 (6) , 515-520
- https://doi.org/10.1093/mutage/3.6.515
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)quinoxaIine (MeIQx), 2-amino-6-methyldipyrido[l,2-a:3′,2′-d]imidazole (Glu-P-1) and 3-amino-l,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.This publication has 20 references indexed in Scilit:
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