标题：Chemical modification of DNA with muta-carcinogens. I. 3-Amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole: metabolic activation and structure of the DNA adducts.
摘要：3-Amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) are potent mutagen/carcinogens isolated from pyrolyzates of tryptophan and glutamic acid, respectively, and they have been found to exist in many cooked foods. Trp-P-2 and Glu-P-1 bind to DNA covalently after metabolic activations. The compounds are oxidized to the corresponding hydroxylamines (N-OH-Trp-P-2 and N-OH-Glu-P-1) by microsomes. N-OH-Trp-P-2 and N-OH-Glu-P-1 are the proximate forms of Trp-P-2 and Glu-P-1, respectively. They are further activated by cytosol to the O-acyl derivatives, which bind covalently with DNA. The structures of the modified nucleic acid bases were identified as 3-(C8-guanyl)amino-1-methyl-5H-pyrido[4,3-b]indole (Gua-Trp-P-2) and 2-(C8-guanyl)amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Gua-Glu-P-1). These initial events caused by Trp-P-2 and Glu-P-1 were established chemically, both in vitro and in vivo. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (812K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 209 210 211 212 213 214
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