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N Inui

Publications and source records attributed to N Inui.

At least 55 records · Page 3Linked to original sources
PubMed1991

Inhibitory effects of radical scavengers on diacylglycerol-promoted transformation in BALB/3T3 cells.

To discover the relationship between the activation of protein kinase C and the generation of reactive oxygen in the tumor promotion process, we investigated the effects of radical scavengers on diacylglycerol-promoted transformation in BALB/3T3 cells. Superoxide dismutase (SOD) showed inhibitory effects on both 1-oleoyl-2-acetylglycerol (OAG)-promoted and diolein-promoted transformation. Catalase (CT) suppressed the promoting effects of diolein by up to 70%. Mannitol (MT), a hydroxyl radical (.OH) scavenger, inhibited diacylglycerol-promoted transformation dose-dependently. These results suggest that activation of protein kinase C alone is insufficient and that generation of reactive oxygen accompanied by activation of the enzyme is essential to the promotion process in BALB/3T3 cells.

Animals↗
PubMed1990

A comparison of micronucleus induction in 3 mouse strains with representative clastogens.

The frequency of micronucleated polychromatic erythrocytes (MNPCEs) was compared in BALB/c, C57BL/6 and DBA/2 mice after the intraperitoneal injection (i.p.) of methyl methanesulfonate (MMS), potassium chromate (K2CrO4), colchicine (COL), cycloheximide (CYH), 4-nitroquinoline-1-oxide (4-NQO) and 5-fluorouracil (5-FU). In BALB/c mice, the frequency of MNPCEs was significantly increased by all the chemicals tested, as compared to the vehicle control. In both C57BL/6 and DBA/2 mice, MMS, K2CrO4, COL and 4-NQO significantly increased MNPCEs, but CYH and 5-FU only slightly increased the MNPCEs in C57BL/6 and had no effect on DBA/2 mice. These results suggest that BALB/c mice are more sensitive to the induction of MNPCEs with a wider spectrum of chemicals than C57BL/6 or DBA/2 mice.

Animals↗
PubMed1990

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-enhanced transformation in vitro by inhibitors of phospholipid metabolism.

The effects of some inhibitors of phospholipid metabolism were studied using a two-stage transformation assay system in vitro with 3-methylcholanthrene (3-MC) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in BALB/3T3 cells. Inhibitors of phospholipid metabolism such as hydrocortisone (HC), p-bromophenacyl bromide (BPB), nordihydroguaiaretic acid (NDGA), quercetin and indomethacin (IM) were used. They were demonstrated to inhibit strongly TPA-promoted transformation. In particular, HC at 1 microgram/ml inhibited the in vitro transformation completely. All the inhibitors used inhibited transformation in a dose-dependent manner. The results suggest that phospholipid metabolism is important for the promotion stage of transformation in BALB/3T3 cells.

Animals↗
PubMed1990

Effects of activators and inhibitors of protein kinase C on two-stage transformation in BALB/3T3 cells.

To determine the relationship between protein kinase C and the promotion of carcinogenesis, we investigated the effects of activators and inhibitors of protein kinase C on two-stage transformation in BALB/3T3 cells. Diacylglycerols, which are activators, and specific inhibitors, such as palmitoyl-DL-carnitine chloride (PC), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), and staurosporine (ST) were used. Treatment with diacylglycerols enhanced focus formation in 3-methylcholanthrene (3-MC)-initiated cells, but not as much as 12-O-tetradecanoylphorbol-13-acetate (TPA). PC and H-7 inhibited TPA-enhanced transformation by 76 and 79%, respectively. ST, the most potent inhibitor of protein kinase C, had a low inhibitory effect on transformation at non-toxic doses (33% inhibition). The results suggest that protein kinase C may play an important role in the process by which transformation is promoted in BALB/3T3 cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

DNA damage induced in mouse peritoneal exudate cells after in vivo administration of chemical and physical agents as determined by alkaline elution.

The alkaline elution technique for detecting DNA strand breaks has been applied to the study of DNA damage in mouse peritoneal exudate cells resulting from the in vivo administration of chemical and physical agents. The direct methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea induced extensive breakage in samples taken 2 h after administration. The direct ethylating agents ethyl methanesulphonate and N-ethyl-N-nitrosourea also induced DNA strand breaks, but to a lesser extent than the methylating agents. The indirect methylating agent dimethylnitrosamine showed hardly any effect in this system. A weak but positive response was observed upon treatment with the anti-neoplastic alkylating agent procarbazine hydrochloride. The whole-body irradiation of mice with 60Co gamma-rays also induced DNA strand breaks. The elution profiles for gamma-ray irradiation were different from those of alkylating agents, and indicate that alkylating agents produce many more secondary lesions leading to DNA strand breaks than gamma-rays. N-methyl-N-nitrosourea produced slightly more DNA strand breaks in mutagen-sensitive mice, which are derived from the CD-1 strain, than in ICR mice.

Alkylating Agents↗
PubMed1990

[Olivocerebellar, corticonuclear and nucleocortical projections in the "four limbs area" of the paramedian lobule in the cat: a combined electrophysiological and HRP study].

The present study examined the olivocerebellar, corticonuclear and nucleocortical projections in the medial and lateral parts of the "four limbs area" of the paramedian lobule in the cat. Each part of the area could be identified electrophysiologically on the basis of their climbing fiber input. A small volume of 20% horseradish peroxidase (HRP) was injected iontophoretically into the center of an identified area. Results obtained are as follows: 1) Labeled cells were found in the rostral one-third of the medial accessory olive (MAO) of the inferior olive following injections of HRP in the four limbs area of the paramedian lobule. 2) The central MAO projects to the medial and lateral parts of the four limbs area in the caudal folium of the rostral part of the paramedian lobule. 3) The lateral and central MAO project to the medial part of the four limbs area in the intermediate part of the paramedian lobule, and the medial and central MAO project to the lateral part of the four limbs area in the intermediate part of the paramedian lobule. 4) The posteromedial three-fifths of the ipsilateral nucleus interpositus posterior (NIP) receive the corticonuclear projections from the four limbs area. 5) The medial two-fifths of the ipsilateral NIP project to the four limbs area. No strict point-to-point reciprocal relationship was found between corticonuclear and nucleocortical projections.

Animals↗
PubMed1989

A comparison of intraperitoneal injection and oral gavage in the micronucleus test with mitomycin C in mice.

Intraperitoneal (i.p.) injection and oral (p.o.) gavage were evaluated in the mouse micronucleus test with mitomycin C (MMC). The tests were carried out in 2 laboratories with the MS/Ae and CD-1 mouse strains. On the basis of a small-scale acute toxicity study and a pilot experiment, the full-scale micronucleus test was performed with a 24-h sampling time at doses of 1, 2, 4, and 8 mg/kg for both treatment routes. In both strains, a clear positive dose-response relation was shown by both routes. Although the frequency of micronucleated polychromatic erythrocytes (MNPCEs) was higher with i.p. on a mg/kg basis, this tendency was reversed when dose was expressed as a percentage of the LD50.

Administration, Oral↗
PubMed1989

[Somatotopic representation of climbing fiber projections from limb cutaneous afferents to the paramedian lobule of the cat cerebellum].

Climbing fiber projections to the cerebellar paramedian lobule were investigated electrophysiologically by stimulation of bilateral superficial radial nerve (SR) and superficial peroneal nerve (SP) in the cat anesthetized with pentobarbitone. In the medial zone of the paramedian lobule, short latency climbing fiber responses to stimulation of the ipsilateral SR were recorded rostrally from the top caudal part of the intermediate folia and short latency responses to stimulation of the ipsilateral SP were obtained caudally from the bottom caudal part of the folia. In the central zone, long latency responses to stimulation of the bilateral SR and SP were obtained. "Four limbs area" in which these responses were recorded was 1.0-1.2 mm in width. Short latency responses to stimulation of the ipsilateral SR were observed rostrally from this area, and short and long latency responses to stimulation of the ipsilateral SP were distributed caudally from this area. In the lateral zone, short and long latency responses to stimulation of the ipsilateral SR were recorded rostrally from the rostral part of the intermediate folia, and long latency responses to stimulation of the ipsilateral SP were observed caudally from the caudal part of the folia. In the most lateral zone, short and long latency responses to stimulation of the ipsilateral SR were obtained rostrally from the rostral part of the intermediate folia, and long latency responses to stimulation of ipsilateral SP were recorded only in the bottom caudal part of the folia caudally from the caudal part of the folia.

Afferent Pathways↗
PubMed1988

Screening for skin-tumor promoters.

Since attention has been drawn to the role of oxygen radicals in tumor promotion, we investigated whether or not the nitroblue tetrazolium (NBT) reduction test using mouse peritoneal macrophages was useful as a rapid screening method for skin-tumor promoters. On the basis of our results, we concluded that this test system was appropriate for the screening of 12-0-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters and bore comparison with other screening methods for tumor promoters. A large number of skin-tumor promoters, such as active phorbol esters, teleocidin and aplysiatoxin, appear to act indirectly through a free radical mechanism by binding to a membrane receptor.

Animals↗
PubMed1987

Mouse strain differences in the induction of micronuclei by polycyclic aromatic hydrocarbons.

The frequency of micronucleated erythrocytes (MNE) in 3 inbred mouse strains and 2 of their hybrids (C57BL/6, BALB/c, DBA/2, BDF1 and CDF1) were examined after polycyclic aromatic hydrocarbons (PAHs; 7,12-dimethylbenz[a]anthracene (DMBA), 3-methylcholanthrene (3-MC), benzo[a]pyrene (BaP), benzo[e]pyrene (BeP) and anthracene (ANT] were injected i.p. PAHs are thought to form active metabolites after being administered to mammals. In mouse strains with inducible PAH activating enzymes, such as C57BL/6 or BALB/c, MNE were significantly induced, as compared to control mice, 48 h after DMBA, BaP, or 3-MC was injected. No increase in the frequency of MNE occurred in the DBA/2 strain which cannot induce the activating enzymes. BeP and ANT did not increase the frequency of MNE in any mouse used. The levels of MNE induction in BDF1 or CDF1 hybrids were similar to those in C57BL/6 or BALB/c. These results support the view that the genetic capacity to metabolize PAHs is strongly associated with micronucleus induction as in the case of PAH carcinogenesis.

Animals↗
PubMed1987

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-enhanced transformation in vitro by radical scavengers.

The inhibitory effects of some scavengers of oxygen radicals were studied, using a two-stage transformation assay system in vitro 3-methylcholanthrene (3-MC)-initiation and 12-O-tetradecanoylphorbol-13-acetate-(TPA)-promotion in Balb 3T3 cells. Mannitol, a scavenger for hydroxyl radicals, strongly inhibited the TPA-enhanced transformation in a dose-dependent manner. Superoxide dismutase (SOD) and catalase, which are specific scavengers for O2-. and H2O2, respectively, also inhibited the transformation. These results suggest that oxygen radicals may play an important role in the TPA-enhanced transformation in Balb 3T3 cells.

Animals↗
PubMed1986

Chromatid aberrations in a novobiocin-resistant subline of Chinese hamster V79 cells after exposure to novobiocin.

We examined effects of novobiocin alone or in combination with gamma-irradiation, on the frequencies of chromatid-type aberrations in a novobiocin-resistant subline of Chinese hamster V79 cells (NOVOr-1). NOVOr-1 cells were significantly resistant to novobiocin, as compared to wild-type V79 (WT) cells, with respect to cell survival and DNA synthesis. Survival responses of WT and NOVOr-1 cells to gamma-rays in the range 2-10 Gy differed only slightly and the number of chromatid aberrations produced by irradiation at 1 Gy was fairly comparable in the two cell types. Post-irradiation treatment of cells with novobiocin at concentrations exceeding 200 micrograms/ml significantly increased the number of chromatid gaps plus breaks in WT cells as compared with NOVOr-1 cells. With 200 micrograms/ml the increase was 1.2-fold (t-test, P less than 0.05) and with 400 micrograms/ml, 2.3-fold (P less than 0.01) the number produced in NOVOr-1 cells.

Animals↗
PubMed1986

Retinoic acid and butylated hydroxyanisole inhibit promoter-enhanced transformation in vitro.

The inhibitory effects of some antipromoters were studied using a two-stage transformation assay system in vitro with 3-methylcholanthrene (3-MC)-initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotion in BALB 3T3 cells. Butylated hydroxyanisole (BHA), a phenolic antioxidant, inhibited TPA-enhanced transformation in a dose-dependent manner, but butylated hydroxytoluene (BHT) did not. Among the three antipromoters tested, retinoic acid (RA) was the most effective inhibitor.

Butylated Hydroxyanisole↗
PubMed1986

Establishment of lung fibroblastic cell lines from a non-human primate Tupaia belangeri and their use in a forward gene mutation assay at the hypoxanthine-guanine phosphoribosyl transferase locus.

The cells obtained from a lung of a new-born male Tupaia belangeri were maintained in mass culture for greater than 400 days. After 55 population doubling levels (100 days in culture), three cell lines were separately established; these lines showed constant growth properties. One line, designated as T-23, was used for a mutation assay. The T-23 cells showed an absolute plating efficiency of 30-50%, and a population doubling time of 18-19 h in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. The cells had a modal chromosome number of 62 (pseudodiploid) with the loss of a chromosome and the gain of an unidentified one. T-23 cells, like human cells, were much more susceptible to ouabain than mouse cells but relatively less susceptible to 8-azaguanine, while, unlike human cells, they were less sensitive to 6-thioguanine (6TG). N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was less, but 4-nitroquinoline-1-oxide (4NQO) was more toxic to T-23 cells than to human or mouse cells. Benzo[a]pyrene-induced toxicity was almost comparable among the cell types. For the mutation assay, we chose 6TG-resistance (100 microM) as a marker. The optimal expression time (8-13 days) and cell density at selection to eliminate metabolic cooperation (2 x 10(4) cells/60-mm dish) were determined. Some of the cells selected with 6TG showed less than 0.4% of the total incorporation of [14C]hypoxanthine into wild-type cells, suggesting the mutants under selection were affected at the hypoxanthine-guanine phosphoribosyl transferase locus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Mouse peritoneal lymphocytes, a new target for analyzing induction of sister chromatid exchanges on in vivo exposure to a genotoxic agent.

The availability of use of mouse peritoneal lymphocytes as target cells for analyzing sister chromatid exchanges (SCE) upon exposure to a genotoxic drug, cyclophosphamide, was investigated using female ICR mice. Use of these cells overcame the difficulty in use of mouse lymphocyte cultures, recovering sufficient metaphase cells. The greatest advantage of use of peritoneal lymphocytes was that about 1-2 X 10(6) lymphocytes/mouse could easily be recovered from the peritoneal cavity in high purity. Their mitogenic responses were good when Escherichia coli lipopolysaccharide, in combination with 2-mercaptoethanol, was used as mitogens, but they were less when purified phytohemagglutinin was used. In the presence of lipopolysaccharide (60 micrograms/ml) and 2-mercaptoethanol (22-88 microM), the maximum incidence of second division metaphases (greater than 50%) and the highest mitotic index (greater than 4%) were observed 36-40 h after stimulation. Under these conditions, the base-line SCE showed the constant level. The range of intrastrain variations in the base-line SCE was 0.24-0.36/chromosome. The distribution histograms of SCE/chromosome did not fit a single Poisson model, suggesting that these cells are heterogeneous with respect to the base-line SCE. Single s.c. injections 1 h before harvest of doses of 0.75-3.0 mg of cyclophosphamide per kg evoked positive responses, and injections of over 0.375 mg/kg had linear dose-dependent effects. On harvest of cells for up to 192 h after the injection, the maximal induction of SCE attained 1 h after exposure was found to return time dependently to the control level at 192 h. After the initial rapid reduction in the cell number, cellular recovery, measured as the mitotic index and the number of peritoneal exudate cells recovered, returned to the control level within 48 h, without a significant increase thereafter. After maintaining cells under the liquid-holding experiment for various times in vitro following a single exposure to cyclophosphamide for 1 h in vivo, the reduction of their SCE and recovery of their mitotic index were more rapid than those of cells in the time-course experiment. These findings suggest that the association of the recruitment of less- and/or nondamaged cells from their precursors with reduction of the SCE is slight. Repair(s) and, to a lesser extent, selective loss of more damaged cells may be the main factors contributing to the early reduction response of the SCE frequency. The relations of these factors are discussed.

Animals↗
PubMed1985

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced nitroblue tetrazolium reduction in mouse peritoneal macrophages by various tumor promotion inhibitors.

The effects of various inhibitors on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced reduction of nitroblue tetrazolium (NBT) in mouse peritoneal macrophages were investigated. The reduction was inhibited by phospholipase A2 inhibitors, such as dibromoacetophenone, the lipoxygenase inhibitor nordihydroguaiaretic acid, an NADH-dehydrogenase inhibitor, the microfilament inhibitor cytochalasin B, oxygen radical scavengers such as superoxide dismutase, antioxidants such as butyl hydroxyanisole and non-specific inhibitors such as retinoic acid. The reduction was not affected by the cyclooxygenase inhibitor indomethacin or the H2O2 scavenger catalase.

Animals↗
PubMed1985

Induction of nitroblue tetrazolium reduction in mouse peritoneal macrophages by tumour promoters and inhibition of the induced nitroblue tetrazolium reduction by some inhibitors.

Two polyacetates, aplysiatoxin and debromoaplysiatoxin, as well as 12-O-tetradecanoylphorbol-13-acetate (TPA), mezerein and teleocidin enhance nitroblue tetrazolium (NBT) reduction in mouse peritoneal macrophages in vitro. The ED50 values for NBT reduction of these 5 TPA-type tumor promoters were 4.2 ng/ml for TPA, 36 ng/ml for mezerein, 0.53 ng/ml for teleocidin, 1.5 ng/ml for aplysiatoxin and 108 ng/ml for debromoaplysiatoxin. The NBT reduction induced by the 5 tumor promoters is inhibited by 2 inhibitors of tumor promotion, retinoic acid and dibromoacetophenone. The possibility that tumor promotion by TPA-type tumor promoters involves similar mechanisms such as superoxide anion radicals release in cell membranes is discussed.

Acetophenones↗