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Biomedical subjects

K Shudo

Publications and source records attributed to K Shudo.

At least 163 records · Page 9Linked to original sources
PubMed1985

Chemical modification of DNA with muta-carcinogens. II. Base sequence-specific binding to DNA of 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1).

2-Amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) binds covalently to DNA after metabolic activation to give 2-(C8-guanyl)amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Gua-Glu-P-1). The importance of the intercalative ability of the Glu-P-1 skeleton into DNA base pairs for this reaction is emphasized. The reactive form of Glu-P-1, N-acetoxy-Glu-P-1 (N-OAc-Glu-P-1), reacts preferentially at the C8 position of guanine residues in G-C-rich regions of DNA.

Base Sequence↗
PubMed1985

Chemical modification of DNA with muta-carcinogens. III. Reductive alkylation of DNA with mitomycin C.

Mitomycin C (MMC) binds to DNA after its reductive activation by catalytic hydrogenation with Pd on charcoal. Three modified nucleotides, named MG-1, MG-2, and MA, were isolated from the modified DNA after enzymatic hydrolysis to 5'-nucleotides. The structures of these modified nucleotides were deduced from their 1H-NMR and UV spectra, and from studies of the chemically transformed derivatives (hydrolysis, methylation, diazotization, and thioketonization). These three modified nucleotides were concluded to be 1,2-trans-2,7-diamino-1-(N2-deoxyguanylyl)mitosene (MG-1), 2,7-diamino-1-(O6-deoxyguanylyl)mitosene (MG-2) and 2,7-diamino-1-(N6-deoxyadenylyl)mitosene (MA). The same modified nucleotides were identified in DNA extracted from the livers of rats treated with MMC.

Alkylation↗
PubMed1985

Two bases are eliminated from DNA by treatment with bleomycin or with hemin-intercalators.

A hemin-intercalator, H4G-His, which possesses 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) as an intercalator moiety and histidine as an intramolecular ligand of the ferrous ion of the hemin ring, cleaves DNA very efficiently, and acts at guanine-pyrimidine sequences preferentially. Bleomycin (BLM) also cleaves DNA with the same base-sequence selectivity shown by H4G-His. The 5'-terminal of the DNA fragments cleaved by H4G-His or by BLM bears a phosphoryl group, while the 3'-terminal of the cleaved DNA fragments does not possess a 3'-phosphoryl group. There are three (or more) kinds of structures of the 3'-terminals. One of the structures of the 3'-terminals of the cleaved DNA fragments is a free 3'-hydroxy group. We propose that there exist plural mechanisms for DNA cleavage by H4G-His or by BLM, one of which involves elimination of two bases from DNA.

Base Sequence↗
PubMed1984

2-Aminodipyrido[1,2-a:3',2'-d]imidazole-porphyrin(Fe) derivatives as sequence specific DNA cleaving reagents.

Some porphyrin (Fe)-intercalators were synthesized. We chose 2-aminodipyrido[1, 2-a:3',2'-d]imidazoles (Glu-P's), which were muta-carcinogens isolated from a pyrolysate of L-glutamic acid, as intercalator moieties. These synthetic porphyrin (Fe)-intercalators cleave DNA at G-C and G-T sequences. The specificity for cleavage of base sequences of DNA is quite similar to that of bleomycin.

Aminopyridines↗
PubMed1984

Studies on olivoretins indicate a requirement for a free hydroxyl group for teleocidin B activity.

Three olivoretins, A, B and C (isolated from Streptoverticillium olivoreticuli), which are O-methylated teleocidin B isomers, were found to be biologically inactive. A fourth olivoretin, D, which has a free hydroxyl group and is identical to one of the four teleocidin B isomers, teleocidin B-4 (teleocidin B of Hirata) was biologically active. These findings indicate that the free primary hydroxyl group of teleocidin B isomers is necessary for activity. The effect on biological activity of the structural difference between des-O-methylolivoretin B (teleocidin B-1) and des-O-methylolivoretin C was also studied.

Animals↗
PubMed1984

Inhibition by hemin of dinitropyrene-induced mutagenesis in Chinese hamster V79 cells.

The inhibitory effects of hemin on the mutagenic activities of 1,3-, 1,6- and 1,8-dinitropyrenes (1,3-,1,6- and 1,8-DNPs) were investigated in Chinese hamster V79 cells. Mutant cells were selected on the basis of their resistance to ouabain. Hemin itself did not have any cytotoxic effect on Chinese hamster V79 cells, and did not induce mutations when added at a concentration of 10 micrograms/ml. The mutagenic activities of 1,3-, 1,6- and 1,8-DNPs were inhibited dose-dependently by hemin and were reduced 91.7%, 95.7% and 94.7%, respectively, by the highest concentration of hemin tested (10 micrograms/ml).

Animals↗
PubMed1984

Structure-activity studies on synthetic analogues (indolactams) of the tumor promoter teleocidin.

Synthetic analogues (indolactams) related to the tumor promoter teleocidin were synthesized chemically. Of four indolactam-Vs lacking the monoterpenoid moiety of native teleocidin, (-)-indolactam-V bound to the 12-O-tetradecanoylphorbol-13-acetate receptor in cell membranes and induced both adhesion of HL-60 cells and ornithine decarboxylase activity in mouse skin, although its effects were weaker than those of teleocidin. (+)-Indolactam-V and two isomers of epi-indolactam-V showed no induction of ornithine decarboxylase. These results indicate that the S,S configuration of native teleocidin at the isopropyl residue and the hydroxymethyl group is necessary for activity.

Animals↗
PubMed1983

Sequence selective modification of DNA with muta-carcinogenic 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole.

2-Acetoxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole binds covalently to the 8 position of guanine residues in DNA. Treatment of the modified DNA with aqueous piperidine causes the liberation of the modified nucleic acid base, 2-(C8-guanyl)amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole, and cleavage of DNA at the sites of the modified guanylic acid residues. By use of 5'-end 32P-labelled DNA and sequence analysing gel electrophoresis, we discovered the base sequence specificity of DNA modification with 2-acetoxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole. The guanine residues in G-C cluster-like regions are modified more frequently.

Base Sequence↗
PubMed1983

Nakahara memorial lecture. New classes of tumor promoters: teleocidin, aplysiatoxin, and palytoxin.

Teleocidin and aplysiatoxin, which are structurally different from 12-O-tetradecanoylphorbol-13-acetate (TPA), were found to be potent tumor promoters in two-step mouse skin carcinogenesis. The class of teleocidin includes dihydroteleocidin B, teleocidin, and lyngbyatoxin A. Teleocidin, which is a mixture of 93% teleocidin A and 7% teleocidin B, was isolated from Streptomyces mediocidicus as a strong skin irritant. Teleocidin A consists of C-14S-teleocidin A and C-14R-teleocidin A. One teleocidin A-isomer corresponds to lyngbyatoxin A, which was isolated from the blue-green alga, Lyngbya majuscula. Teleocidin B has four isomers, C-14, C-17-diastereomers. The two teleocidin A-isomers and three of the teleocidin B-isomers (all but one, which was obtained in too low yield) were shown to be biologically active and also potent tumor promoters. Synthetic analogues (indolactams) of teleocidin were obtained and their structure-activity relations were examined by several biological tests. The finding that only (-)-indolactam-V was active showed that the S, S configuration of native teleocidin was necessary for expression of the activity. The class of aplysiatoxin, which was isolated from the blue-green alga, L. majuscula, includes debromoaplysiatoxin, aplysiatoxin, bromoaplysiatoxin, and oscillatoxin A (nordebromoaplysiatoxin). The former three were potent tumor promoters, while oscillatoxin A was a moderate one. Dibromoaplysiatoxin, which is a chemically brominated derivative of debromoaplysiatoxin, in addition to aplysiatoxin and bromoaplysiatoxin, possessed the same promoting activity as that of oscillatoxin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylamides↗
PubMed1982

Modification of nucleic acids with muta-carcinogenic heteroaromatic amines in vivo. Identification of modified bases in DNA extracted from rats injected with 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-6-methyldipyrido[1,2-a3:3',2'-d]imidazole.

Potent muta-carcinogens isolated from amino-acid pyrolysates, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-1-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), were injected intraperitoneally into Male Wistar rats. DNA and rRNA modified with these muta-carcinogens were then extracted from the livers of the rats, and modified nucleic-acid bases were isolated and analysed by high-performance liquid chromatography (HPLC). These 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) by comparison of their retention times on HPLC and UV spectra with those of authentic compounds.

Animals↗