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Biomedical subjects

M Ohsawa

Publications and source records attributed to M Ohsawa.

At least 217 records · Page 12Linked to original sources
PubMed1987

Involvement of DNA polymerases in the repair of DNA damage by benzo[a]pyrene in cultured Chinese hamster cells.

Mechanisms for induction of single-strand scissions in DNA by S9-activated benzo[a]pyrene (B[a]P) and their repair in cultured Chinese hamster V79 cells were investigated with inhibitors of DNA-repair synthesis using alkaline sucrose gradient sedimentation analysis. The marked induction of single-strand scissions in DNA was observed following 3 h treatment of V79 cells with 5 micrograms/ml of B[a]P. These DNA lesions were repaired to the control level within 4 h after removal of B[a]P. The simultaneous addition of inhibitors of DNA-repair synthesis. 1-beta-D-arabinofuranosylcytosine (araC) plus hydroxyurea with B[a]P did not increase the formation of DNA single-strand scissions. When these inhibitors were added after removal of B[a]P, however, they significantly blocked the rejoining of DNA-strand scissions. On the other hand, when aphidicolin, a specific inhibitor of DNA polymerase alpha, was used instead of araC, a partial inhibition of the rejoining was observed, and further addition of 2',3'-dideoxythymidine, an inhibitor of DNA polymerase beta, augmented the inhibitory effect. These results indicate that B[a]P-induced single-strand scissions of DNA in V79 cells could be repaired mostly by excision repair which involved DNA polymerase alpha and a non-alpha polymerase, presumably polymerase beta.

Animals↗
PubMed1987

Host-mediated antitumor effect of grifolan NMF-5N, a polysaccharide obtained from Grifola frondosa.

The antitumor mechanism of grifolan NMF-5N, a beta-1,3-glucan obtained from mycelia of Grifola frondosa, was examined. Grifolan NMF-5N did not show direct cytocidal effect on cultured tumor cells. However, intraperitoneal injection of grifolan NMF-5N increased the number of peritoneal exudate cells and peritoneal adherent cells which showed cytostatic activity towards syngeneic tumor cells. In an in vivo assay, the administration of carrageenan, an inhibitor of macrophage function, reduced the antitumor activity of grifolan NMF-5N. The delayed-type hypersensitivity reaction was augmented in the grifolan NMF-5N-administered mice. The administration of NMF-5N augmented the induction of cytotoxic T cells but the antitumor activity of grifolan NMF-5N was reduced in athymic nu/nu mice. In addition, the treatment with anti-Thy 1,2 antibody and complement C' of spleen cells taken from mice which showed regression of tumor due to grifolan NMF-5N, reduced the neutralizing effect in Winn assay. These results suggested that grifolan NMF-5N shows antitumor activity via host-mediated mechanisms and both macrophages and T cells play important roles in the mechanisms.

Animals↗
PubMed1986

Strain differences in cadmium-mediated suppression of lymphocyte proliferation in mice.

Strain differences were investigated on the proliferative responses of splenic lymphocytes obtained from C3H/He, BALB/c, and DBA/2 mice that were treated with cadmium (Cd) for 5 days (0.5 or 1.0 mg Cd/kg/day, sc), and the results were compared with those of in vitro treatment of spleen cells with Cd. Following in vivo treatment, splenocytes from the C3H strain were significantly more susceptible to suppressive effects of Cd exposure on all indices for proliferative responses to mitogens (concanavalin A, phytohemagglutinin, and lipopolysaccharide) and allogeneic lymphocytes, while those from DBA and BALB strains were fairly resistant. Among the three strains, the highest Cd concentrations in plasma and spleen were obtained in the C3H strain with the lowest hepatic concentration of Cd. On the other hand, the Cd exposure hardly affected the splenic concentration of zinc in the C3H strain in contrast to its decrease in the others. When spleen cells obtained from normal mice were treated in vitro with Cd, the C3H strain was more resistant to the suppressive effect of Cd than the other strains. These results indicate that the mouse strain variations in Cd-mediated suppression of lymphocyte proliferation are not based on intrinsic lymphocyte sensitivities, but likely are due to differences in the metabolism of Cd, which is under genetic control.

Animals↗
PubMed1986

Determination of serum delta 5-3 beta-hydroxysteroid sulphates by combined high-performance liquid chromatography and immobilized 3 beta,17 beta-hydroxysteroid dehydrogenase in column form.

We studied the use of an immobilized enzyme, covalently bound to aminopropyl-CPG, in the analysis of individual delta 5-3 beta-hydroxysteroid sulphates. A microcolumn with immobilized 3 beta,17 beta-hydroxysteroid dehydrogenase was prepared and used together with high-performance liquid chromatography (HPLC). The reduced nicotinamide-adenine dinucleotide produced from delta 5-3 beta-hydroxysteroids by this enzyme was fluorimetrically determined. The immobilized enzyme was sufficiently stable for at least one month or for 180 tests when used repeatedly. A clinical trial demonstrated that this HPLC-immobilized enzyme method is superior to the soluble enzyme method, giving reliable and reproducible results at a low cost.

Adult↗
PubMed1986

Effect of 3-aminobenzamide on the process of ultraviolet-induced DNA excision repair.

The effect of 3-aminobenzamide, a potent inhibitor of poly(ADP-ribosyl)ation, on UV-induced DNA excision repair was investigated. HeLa cells were treated with DNA replication inhibitors, hydroxyurea (HU) and 1-beta-D-arabinofuranosyl cytosine (araCyt), before and after ultraviolet light (UV) irradiation, to accumulate DNA single-strand breaks. The activity of poly(ADP-ribosyl)ation measured in the permeable cell system of HeLa cells was enhanced in a UV dose-dependent manner after the combined treatment with HU and araCyt in vivo. However, DNA repair synthesis in vitro was not affected by addition of 1 mM 3-aminobenzamide or nicotinamide, while incorporation of [3H]NAD in the same system was completely inhibited. Furthermore, neither the magnitude of UV-induced DNA single-strand breaks accumulated by the combined treatment of HU and araCyt nor the rate of their rejoining after release from the HU and araCyt block were influenced even in the presence of 10 mM 3-aminobenzamide. As the cytotoxicity of UV irradiation was significantly potentiated by 5 mM 3-aminobenzamide, these results suggest that poly(ADP-ribosyl)ation is involved in a process other than DNA excision repair induced by UV irradiation.

Adenosine Diphosphate Ribose↗
PubMed1986

Induction of alkaline-labile sites in DNA by benzo [a]pyrene and the repair of those lesions in cultured Chinese hamster cells.

Formation of alkaline-labile sites in DNA by S9-activated benzo [a]pyrene (B [a]P) and the repair of those lesions were investigated using the technique of alkaline elution in cultured Chinese hamster V79 cells. When the cells were treated with B [a]P (1-5 micrograms/ml) there was negligible increase in DNA elution at pH 12.1 as compared to untreated controls. However, the elution of DNA increased at pH 12.6 with a concentration dependency, thereby indicating formation of alkaline-labile sites in DNA by B [a]P. After 4 h of repair incubation the elution of DNA at pH 12.6 of B [a]P (5 micrograms/ml) treated cells returned to the control levels. The half-life of alkaline-labile sites formed by B [a]P was approximately 1.5 h. Inhibitors of DNA-repair synthesis, hydroxyurea (HU) and 1-beta-D-arabinofuranosyl cytosine (ara-C) when added simultaneously with S9-activated B [a]P for 3 h showed an increase in elution of DNA at pH 12.1, indicating that a population of B [a]P-induced DNA lesions could be removed by a rapid DNA-repair process. These results indicate that at least two kinds of DNA lesions, repairable alkaline-labile sites and rapidly repairable DNA single-strand breaks, are detected after B [a]P treatment by the use of the alkaline elution procedure, by changing elution pH.

Animals↗
PubMed1986

Antitumor activity of a beta-1,3-glucan obtained from liquid cultured mycelium of Grifola frondosa.

The antitumor activity of a branched beta-1,3-glucan "grifolan LE" purified from liquid cultures of Grifola frondosa (Ohno et al. Chem. Pharm. Bull., 34, 1709-1715 (1986] was examined on an allogeneic murine tumor system. By intraperitoneal (i.p.) administration (100-200 micrograms/mouse/d X 5) at days 1 to 9 from the tumor transplantation, grifolan LE showed marked inhibitory activity on the growth of solid form sarcoma 180 in ICR mice. Significant activity was also observed in intravenous (i.v.) or intratumoral (i.t.) administrations. However, the oral (p.o.) administration of grifolan LE was not effective. I.p. administration of grifolan LE at a dose of 100 micrograms/mouse/d X 5 before the tumor transplantation showed significant inhibition of tumor growth. I.p. administration of grifolan LE at day +11 to +19 was also effective. Grifolan LE was not effective on the ascites form of sarcoma 180. The pretreatment of sarcoma 180 cell with grifolan LE in vitro did not affect tumor growth. The mice cured from the solid form of sarcoma 180 by administration of grifolan LE had the ability to reject the same tumor cell. From these results, it is suggested that the antitumor activity of grifolan LE occurred by modification of biological responses.

Animals↗
PubMed1986

Clinico-pathological changes induced in rats treated with amine-curing agent for epoxy resin, bis(4-amino-3-methylcyclohexyl)methane.

Amine-curing agent for epoxy resin, bis(4-amino-3-methyl-cyclohexyl)methane (commercial name; Laromin C) has been suspected to have induced in the workers some toxic signs such as collagen disease like scleroderma or polymyositis. Subacute toxicity of this agent was studied in rats following repeated oral administration. The agent was given orally at 5 dose levels (25 mg/kg to 100 mg/kg per one dose) for periods ranging from 10 days to 4 weeks. After the completion of administration, clinico-biochemical tests and histopathological examinations were carried out. In a few cases, skeletal muscles and choroid plexus of the brain were examined by electronmicroscopy. Clinico-biochemical tests revealed some elevation of muscle-derived components such as GOT and CPK as seen in the myopathic diseases. Histologically, various degrees of atrophy, degeneration and regeneration of muscle fibers and a numerical increase of interstitial cells were observed in the skeletal muscles. Electronmicroscopical examination of the gastrocnemius muscle revealed intrasarcoplasmic osmiophilic round-shaped inclusion bodies, sometimes with lamellar structure, which were suggestive of some lipidosis. The epithelial cells of choroid plexus in the brain ventricles represented various degrees of vacuolar changes lightmicroscopically, which were suggested to be dilated smooth endoplasmic reticulum electronmicroscopically. Although scleroderma-like changes were not observed in our experiments, the results suggest that this amine-curing agent for epoxy resin could be one of the causative agents which induced toxic lesions like some collagen diseases including muscle lesions in the workers. In addition, it is considered that the agent may have systemic toxic effects.

Animals↗
PubMed1986

Role of sex-hormone-binding globulin and free sex steroid hormones in hyperandrogenic anovulation.

To clarify the mechanism of hyperandrogenic anovulation, the binding capacity of sex-hormone-binding globulin (SHBG-BC), the levels of free steroid hormones, and the levels of basal serum testosterone (T), estradiol (E2), estrone (E1) and gonadotropins were determined in 42 hyperandrogenic anovulatory women. The mean levels of basal T (0.74 +/- 0.04 ng/ml, p less than 0.001), free T (3.07 +/- 0.51 ng/dl, p less than 0.01) and free E2 (2.26 +/- 0.27 pg/ml, p less than 0.05), basal luteinizing hormone (LH) (33.4 +/- 2.7 mIU/ml, p less than 0.001), responsiveness of LH (180.7 +/- 21.5 mIU/ml, p less than 0.001) after luteinizing hormone releasing hormone (LHRH) administration, and the basal LH/basal follicle stimulating hormone (FSH) ratio (3.42 +/- 0.25, p less than 0.001) in the patients were significantly higher, the SHBG-BC level (1.76 +/- 0.33 micrograms DHT bound/dl, p less than 0.05) significantly reduced, and basal levels of E2 (38.0 +/- 3.2 pg/ml) and E1 (110 +/- 13 pg/ml) unchanged compared to the controls. These findings suggest that increased T in hyperandrogenic anovulatory women results in decreased SHBG-BC and increased free T and E2 which might be the cause of inappropriate gonadotropin secretion followed by chronic anovulation.

Acne Vulgaris↗