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Biomedical subjects

M Miyaki

Publications and source records attributed to M Miyaki.

At least 91 records · Page 5Linked to original sources
PubMed1983

Mechanism of increased susceptibility to 4-nitroquinoline-1-oxide in cultured skin fibroblasts from patients with familial polyposis coli.

About 50% of the strains of cultured fibroblasts from patients with familial polyposis coli (FPC) exhibited increased susceptibility to cytotoxicity of 4-nitroquinoline-1-oxide (4NQO) compared with cells from normal individuals. The FPC cells that showed hyper-sensitivity to 4NQO were also hyper-sensitive to mitomycin C (MMC), but susceptibilities of these cells to UV radiation, methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were within the normal range. The extent of single-strand scission of DNA in the 4NQO-sensitive FPC cells was greater than in normal cells, and the amount of [14C]4NQO bound to DNA in the FPC cells was twice as high as in normal cells. The rate of release of [14C]4NQO from DNA by the post-culture was the same as in both FPC and normal cells. The 4NQO-sensitive FPC cells exhibited increased 4NQO-reductase activity; the level of this activity was consistent with the extent of the decrease in colony formation by 4NQO. These results suggest that the enhanced ability to activate 4NQO might be an important factor in the mechanism of susceptibility of FPC cells to 4NQO rather than the reduced ability to repair DNA.

4-Nitroquinoline-1-oxide↗
PubMed1983

Susceptibility of skin fibroblasts from patients with retinoblastoma to transformation by murine sarcoma virus.

Cultured skin fibroblasts from patients with retinoblastoma (RB) of different etiology have been studied for their susceptibility to transformation by murine sarcoma virus. The cells from patients with a deletion in chromosome 13 (13q-) and those from sporadic unilateral cases due to somatic mutation were as sensitive as normal cells. However, the cells from familial cases showed an extremely high sensitivity to transformation. Moreover, in familial cases the susceptibility was significantly higher in bilaterally affected patients than in unilateral cases. These findings suggest that the heritable RB gene is different from 13q- and its degree of expression is also manifest at the cellular level.

Cell Transformation, Viral↗
PubMed1982

Morphologic transformation and chromosomal changes induced by chemical carcinogens in skin fibroblasts from patients with familial adenomatosis coli.

Skin fibroblasts from patients with familial adenomatosis coli (AC) and normal individuals were treated once with the carcinogen 4-nitroquinoline 1-oxide or N-methyl-N'-nitro-N-nitrosoguanidine and then passaged sequentially. Morphologically altered cells appeared in the cultures of carcinogen-treated AC fibroblasts at passages 6-8 (days 100-140) after treatment with the carcinogens, but carcinogen-treated normal cells and untreated AC and normal cells did not become altered even after cultivation for 25 passages. The cultures containing morphologically altered cells showed characteristics of transformed cells, such as a high frequency of colony formation in soft agarose, increased growth ability, and chromosomal abnormalities. The results suggest tha AC patients have increased susceptibility to morphologic transformation and chromosomal changes induced by chemical carcinogens.

4-Nitroquinoline-1-oxide↗
PubMed1980

Increased sensitivity of fibroblasts of skin from patients with adenomatosis coli and Peutz-Jegher's syndrome to transformation by murine sarcoma virus.

Skin fibroblasts from family members of cases of adenomatosis coli (AC) and Peutz-Jegher's syndrome (PJ) were examined for susceptibility to morphological transformation by Moloney murine sarcoma virus (MSV) of rate 78AI cells, which was found in the present study to contain both dualtropic and ecotropic murine leukemia virus (MLV). The fibroblasts from individuals with manifest AC (22 subjects) and manifest PJ (5 subjects) were up to 5 times more susceptible to transformation by rat 78AI-MSV(MLV) than those from normal individuals (7 subjects). Nonmanifest members of AC families (8 subjects) showed various sensitivities: the fibroblasts from 3 family members had a sensitivity as low as that of normal cells, and those of 5 individuals exhibited increased sensitivity similar to that of manifest cases of AC. The AC and PJ cells that were sensitive to 78AI-MSV(MLV) were also susceptible to transformation by other pseudo-types of Moloney MSV, although they were not transformed by infection of standard Moloney MSV. None of the fibroblasts were transformed by xenotropic MLV alone. The tumor promoter 12-O-tetradecanoyl phorbol-13-acetate enhanced transformation by 78AI-MSV(MLV) in both AC and normal cells.

Adenoma↗
PubMed1979

Mutagenicity of metal cations in cultured cells from Chinese hamster.

The mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) locus in Chinese hamster V79 cells induced by metal cations were examined by the development of resistance to 8-azaguanine (8AG). The spontaneous frequency of 8AG resistance was 5.8 per 10(6) cells, and the frequency was enhanced to 2-6 times that of the control by treatment of cells with the chlorides of beryllium and manganese. About 75% of 8AG-resistant colonies were sensitive to amethopterin, and 86% of the resistant colonies showed less than 3% of the HGPRTase activity of the wild-type cells. The mutant frequency in cultures treated with cobalt and nickel chlorides were slightly increased, and mutation induction was only detectable at very low rates of cell survival.

Animals↗
PubMed1977

Strand breaks of mammalian mitochondrial DNA induced by carcinogens.

Closed circular mitochondrial DNA in mammalian cells was degradated to the open circular form by exposure of the cells to the carcinogens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline 1-oxide (4NQO). MNNG caused more strand scission of mitochondrial DNA than 4NQO at the same concentration. The action of the carcinogens on mitochondrial DNA did not parallel that with nuclear DNA which was damaged by 4NQO more markedly than by MNNG. Mitochondrial DNA damaged by carcinogens was not repaired during 4-20 h of post-treatment incubation of the cells. Incorporation of labeled thymidine into the closed circular mitochondrial DNA, decreased by the treatment of cells with carcinogens, recovered during post-treatment incubation.

4-Nitroquinoline-1-oxide↗
PubMed1976

Actions of bleomycin on DNA ligase and polymerases.

Bleomycin inhibited the ligase, which was partially purified from rat ascites hepatoma, AH-130, even at a concentration as low as 0.01-1 mug/ml. The DNA degraded by bleomycin was not repaired by ligase. Therefore, it was suggested that bleomycin at higher concentration produced strand scission of DNA, which could not be repaired by the ligase, and at lower concentration inhibited the ligase reaction presumably by binding to DNA strand or to ligase. Also, the specificity of inhibition by bleomycin on the DNA polymerase of oncogenic RNA virus was tested, comparing with the four kinds of DNA polymerases extracted from the spleen of mice infected with Friend virus. Three kinds of DNA polymerases from spleen were not inhibited by bleomycin, but the fourth enzyme, which was induced in the spleen by virus infection, was inhibited by the antibiotic, when poly-d(AT) and poly-dG with dC were used as template.

Animals↗
PubMed1975

Binding of bleomycin to DNA in bleomycin-sensitive and -resistant rat ascites hepatoma cells.

The 14C activity of [14C]bleomycin bound to DNA in bleomycin-sensitive rat ascites hepatoma cells (AH-66) was 8.7 times higher than in resistant cells (AH-66F) when the cells were incubated with [14C]bleomycin. The difference in permeability to bleomycin was not significant; uptake of [14C]bleomycin by the sensitive cells was only 1.2 times larger than that by the resistant cells, and the radioactivity incorporated into the nuclei of sensitive cells was only 1.3-fold greater. The bleomycin-inactivating enzyme level in the resistant cells was 3.5 times higher than in the sensitive cells, indicating that the antibiotic incorporated into the resistent cells was reduced in DNA-binding activity to a large extent. The level of protein-free thiol compound in the sensitive cells was 1.8-fold higher than in the resistant cells, suggesting a possible enhancement of bleomycin action by intracellular thiol compound as is found in vitro. These factors probably affect the DNA strand scission and the sensitivity of cells to this antibiotic. Binding of [14C]bleomycin to DNA in vitro was studied in the presence and the absence of dithiothreitol. A large portion of the radioactivity bound in the presence of dithiothreitol was unstable to acid, but the acid-resistant binding was also enhanced by this thiol compound.

Animals↗