Biomedical subjects

M Tajima

Publications and source records attributed to M Tajima.

366 records · Page 21Linked to original sources

PubMedDate not supplied

Effects of luteinizing hormone-releasing hormone analogue on DNA synthesis in rat prostate and uterus.

Buserelin, a potent LH-RH agonist, has been used for the treatment of hormonal disorders such as precocious puberty, endometriosis, cystic mastitis and prostatic carcinoma. Prolonged treatment with buserelin has been known to induce a refractory phase of pituitary desensitization. In the present study, we found that two-week treatment with buserelin strongly suppressed the activities of thymidylate synthetase and thymidine kinase, and markedly reduced the appearance of BrdU-immunoreactive (S-phase) cells in both prostate glands and uteri in male and female adult rats, respectively.

Animals↗

PubMedDate not supplied

Effects of methylglyoxal bis (cyclopentylamidinohydrazone) (MGBCP) on cell cycle progression in three human osteosarcoma cell lines.

Our previous experiments have indicated that the antitumor effects of a polyamine biosynthetic inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), on human osteosarcoma cell lines such as MG-63, G-292 and HOS cells are obtained by its action depleting the cellular polyamine contents. In the present study, the effects of polyamine depletion by MGBCP on the cell cycle progression in these osteosarcoma cell lines were investigated by flow cytofluormetric analysis. MGBCP arrested the tumor cells at the G1 phase by preventing the G/S phase transition. Mitotic indexes (MIs) in these MGBCP-inhibited tumor cells were also decreased. These findings suggest that MGBCP suppresses the cell cycle progression in osteosarcoma MG-63, G-292 and HOS cells by inhibiting intracellular polyamine biosynthesis.

Antineoplastic Agents↗

PubMedDate not supplied

Induction of apoptotic cell death in three human osteosarcoma cell lines by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP).

Our previous experiments have shown that methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a polyamine synthesis inhibitor, suppresses the growth of osteosarcoma cells repressing their intracellular polyamine levels, and that this inhibition of cell growth is only partially reversed by the addition of polyamines. In the present study, we found evidence indicating that the incomplete recovery of cell growth by the addition of polyamines to the polyamine-depleted cells was due to programmed cell death (apoptosis) induced by MGBCP. Morphological changes showing blebbing and chromatin condensation were observed in MGBCP-treated cells, and hypodiploid subpopulations containing apoptotic cells were clearly visible in the profile of flow cytometric analysis. Characteristic oligonucleosomal-sized fragments were increased as the concentration of MGBCP was increased. The results presented here suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in three human osteosarcoma cell lines.

Apoptosis↗

PubMedDate not supplied

Effect of metals and their antagonists on the radical intensity and cytotoxicity of ascorbates.

Five heavy metal antagonists were compared for their specificity of chelating action against copper (CuCl, CuCl2) and iron (FeCl2, FeCl3). ESR spectroscopy showed that both copper and iron significantly enhanced the radical intensity of ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA). Equimolar concentrations of dimercaprol efficiently chelated all these metals, thus significantly reducing their stimulation effects. On the other hand, the chelating action of penicillamine, ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid was limited to CuCl and CuCl2 whereas deferoxamine mesylate (DFO) was a specific iron chelator. The cytotoxic activity of sodium ascorbate was augmented by DFO, but diminished by FeCl3. The simultaneous addition of DFO and FeCl3 counteracted each other, thus neutralizing their individual effects. The cytotoxic activity of both sodium ascorbate and SBA was significantly enhanced by CuCl2 and this stimulation effect of CuCl2 was effectively chelated by DTPA. The present study demonstrates the specificity of the chelating action of these five antagonists, suggesting the possible application of these different types of antagonists for the prevention of the pathogenic diseases catalyzed by the corresponding metals.

Ascorbic Acid↗

PubMedDate not supplied

Role of hydrogen peroxide for cell death induction by sodium 5,6-benzylidene-L-ascorbate.

The role of hydrogen peroxide in the induction of cell death in human promyelocytic leukemic HL-60 cells by sodium 5,6-benzylidene-L-ascorbate (SBA) and its degradation product, ascorbic acid, was investigated. Millimolar concentrations of these compounds induced cell death, characterized by cell shrinkage, nuclear and internucleosomal DNA fragmentation, disappearance of microvilli and condensation of chromatin near the nuclear membrane. Catalase significantly reduced the cytotoxic activity of these compounds, whereas superoxide dismutase, nitric oxide (NO) generator, NO scavenger and NO synthase inhibitor were inactive, suggesting the possible role of H2O2. Determination of H2O2 with the peroxyoxalate chemiluminescence demonstrated that sodium ascorbate and SBA produced H2O2 in amounts necessary for cell death induction.

Antineoplastic Agents↗

PubMedDate not supplied

Re-evaluation of the culture condition of polymorphonuclear cells for the study of apoptosis induction.

The culture conditions of human peripheral blood polymorphonuclear leukocytes (PMN) in the study of apoptosis induction were re-evaluated. The changes in the relative viable cell number of PMNs after tumor necrosis factor (TNF) treatment were colorimetrically investigated using a cell counting kit. The relative potency of PMNs to produce the superoxide anion (O2-) was measured as the reduction of color intensity by addition of superoxide dismutase (SOD). When the PMNs were cultured in conventional RPMI1640 medium supplemented with 10% fetal bovine serum (FBS), the stimulation effect of TNF on O2- generation by PMNs was observed only for the first 6 hours. When FBS was replaced with human serum, the effect of TNF was maintained for longer incubation periods. Prolonged incubation of PMNs spontaneously produced large DNA fragments, and the extent of DNA fragmentation was relatively smaller in human serum-containing medium. TNF, LPS, hyperthermia or potassium thiocyanate slightly accelerated the production of large DNA fragments, as well as the induction of trace amounts of internucleosomal DNA cleavage in PMNs, which became detectable only after concentration by fractional isopropanol precipitation. The present study suggests the importance of the use of human serum rather than conventional FBS for the study of apoptosis induction in PMNs.

Animals↗