Alkylation of DNA with a mitomycin derivative, 7-N-(p-hydroxyphenyl)-mitomycin C. Reductive alkylation nd preferential binding to adenine.
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Biomedical subjects
Publications and source records attributed to K Shudo.
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Mitomycin C (MMC) was catalytically reduced in the presence of a nucleotide or calf thymus DNA. Reaction with 5'-guanylic acid (5'-GMP) gave 1,2-cis-2, 7-diamino-1-(5'-guanylyl) mitosene. Reaction with calf thymus DNA gave modified DNA, which on enzymatic hydrolysis gave two alkylated 5'-deoxyguanylic acid (MG-1 and MG-2) and an alkylated 5'-deoxyadenylic acid (MA). This is the first example of isolation of nucleotides from DNA modified by MMC.
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The mutagenicities of 2-aminodipyrido [1,2-a:3',2'-d] imidazole (Glu-P-2, a mutagen obtained from pyrolysate of glutamic acid) and six methyl substituted derivatives of Glu-P-2 were tested with Salmonella typhimurium TA98 and TA100 with S-9 mix. Glu-P-1 (6-Me-Glu-P-2) was the strongest mutagen to TA98 and TA100. 3-Me-Glu-P-2 was weakest. The presence of a methyl group, and its position were shown to affect the mutagenicity significantly.
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Two potent mutagens, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), isolated from a tryptophan pyrolysate, and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), isolated from a glutamic acid pyrolysate, modified calf thymus DNA in the presence of rat liver microsomes. The major base modified by Trp-P-2 was identified wih 3-(3-guanyl)amino-1-methyl-5H-pyrido[4,3-b]indole. The major base modified by Glu-P-1 was identified with 2-(8-guanyl)amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole. N-acetoxy-Glu-P-1 efficiently modified DNA without microsomes.
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