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Biomedical subjects

N Sawada

Publications and source records attributed to N Sawada.

At least 163 records · Page 9Linked to original sources
PubMed1986

Induction of a novel Ca2+-dependent chymotrypsin-like serine protease by tumor promoters in rat livers.

Induction of a microsomal Ca2+-dependent serine protease by hepatic tumor promoters was studied. Male F344 rats were fed a diet containing one of the following promoting agents: phenobarbital (CAS: 50-06-6), dichlorophenyltrichloroethane (CAS: 50-29-3), butylated hydroxytoluene, ethyl-alpha-chlorophenoxyisobutyrate (CAS: 128-95-0), or 17-alpha-ethynylestradiol (CAS: 57-63-6) or a nonpromoting agent, diphenylhydantoin (CAS: 57-41-0), for 1 week. By treatment with promoters, the protease activity in the microsomal fraction was increased to threefold to fivefold that of control, whereas only a slight increase of activity was found after diphenylhydantoin treatment. The Ca2+-dependent protease activity was determined with the use of N-benzoyl-L-tyrosine ethyl ester as the substrate in a medium containing 50 mM CaCl2 for its maximal activity. This protease was preferentially localized in the smooth microsomal membrane and strongly inhibited by diisopropyl phosphorofluoridate (CAS: 55-91-4), and the optimum pH of the activity was 7.8. It appears that the Ca2+-dependent serine protease measured by using a chymotrypsin substrate is a novel protease, and induction of its activity by hepatic tumor-promoting agents is a common and specific phenomenon.

Animals↗
PubMed1984

Properties of peroxisomes and their induction by clofibrate in normal adult rat hepatocytes in primary culture.

Alterations in peroxisomes and catalase activity and their responsiveness to clofibrate in adult rat hepatocytes in primary culture were investigated. The numbers of peroxisomes with and without crystalloid nucleotids per unit cytoplasmic area were preserved in cultured hepatocytes for 2 d after seeding at a level comparable to that of freshly isolated hepatocytes. At Day 3 in culture, the number of anucleoid peroxisomes was reduced in untreated hepatocytes, accompanied by more significant reduction in the number of nucleoid-containing peroxisomes, which decreased until Day 5. Peroxisome diameters were reduced in untreated hepatocytes at Day 2 and this decrease in the diameter was continued until Day 7. Catalase activity in untreated hepatocytes decreased markedly with culture age. The number of anucleoid peroxisomes was significantly greater in hepatocytes treated with 2 mM clofibrate in culture than in freshly isolated hepatocytes for 2 d or in untreated hepatocytes of the same culture age through 7 d. The number of nucleoid-containing peroxisomes in the treated cells began to decrease in 3 d, but was greater than that of untreated cells at Days 3 and 5. Peroxisomes with well-developed nucleoids were observed frequently in the treated cells even at Day 7. Peroxisome diameters were greater in the treated cells than in untreated cells at Days 3, 5, and 7. Catalase activity was always higher in the treated cells than in untreated cells. These results suggest that clofibrate is effective in inducing peroxisome proliferation as well as in maintaining the organelles in cultured hepatocytes.

Animals↗
PubMed1983

Effect of simultaneous administration of clofibrate with diethylnitrosamine on hepatic tumorigenesis in the rat.

Effect of clofibrate administered simultaneously with diethylnitrosamine (DEN) on hepatocarcinogenesis in F344 male rats was investigated. DEN was given in drinking water at a concentration of 40 ppm for 5 weeks. Rats were fed the diet containing clofibrate at concentrations of 0.1% and 0.25% during DEN-treatment. All rats were killed 25 weeks after the beginning of DEN-treatment, and hepatic tumors over 1 mm in diameter were counted. Hepatic tumors in the rats given clofibrate at both concentrations were twice as many as those in rats given DEN alone. The significant increase in number of hepatic tumors was observed mainly in the tumors under 10 mm in diameter. Thus, the enhancing effect of clofibrate on hepatocarcinogenesis was evident even when fed simultaneously with the carcinogen, in contrast with phenobarbital (PB).

Animals↗
PubMed1983

Effects of phenobarbital-feeding on the phalloidin-sensitivity of rat hepatocytes.

Male F344 rats were continuously fed 0.05% phenobarbital (PB)- or 0.02% 2-acetylaminofluorene (2-AAF)-containing diet for 3 or 8 weeks. The hepatocytes were isolated by a collagenase-perfusion technique and changes in the phalloidin-sensitivity of the cells were examined. After an 8-week treatment with PB or 2-AAF, the phalloidin-sensitivity, in terms of formation of cytoplasmic blebs over the cell surface, was reduced significantly in both groups. The degree of insensitivity to phalloidin induced by PB was found to be similar to that induced by 2-AAF. Two weeks after cessation of the PB-feeding, the sensitivity had recovered to the control range, while the decreased sensitivity induced by 2-AAF persisted for at least 2 weeks after the cessation of 2-AAF-feeding. Furthermore, cytochemical examinations of normal and 2-AAF-treated hepatocytes revealed that the degree of sensitivity decreased in the order of normal hepatocytes, 2-AAF-treated gamma-glutamyl transpeptidase-negative hepatocytes, and 2-AAF-treated gamma-glutamyl transpeptidase-positive hepatocytes. The decreased sensitivity of the latter two cell types also persisted for 2 weeks after the cessation of carcinogen treatment.

2-Acetylaminofluorene↗
PubMed1983

Elevation of gamma-glutamyl transpeptidase activity in rat liver induced by feeding of butylated hydroxytoluene.

The effect of butylated hydroxytoluene (BHT) on gamma-glutamyl transpeptidase (GGT) activity in F344 rat liver was investigated. GGT activity was significantly higher after the 1st week of BHT feeding than in control rats, and the high activity was maintained until BHT feeding was stopped. Four weeks after the cessation of an 8-week course of BHT feeding, there was no difference in liver GGT activity between control rats and BHT-treated rats. Histochemical analysis showed that GGT-positive hepatocytes appeared in periportal areas of the liver lobules in BHT-treated rats.

Animals↗
PubMed1982

Effects of various concentrations of ethyl-alpha-p-chlorophenoxyisobutyrate (clofibrate) on diethylnitrosamine-induced hepatic tumorigenesis in the rat.

Male F344 rats were given diethylnitrosamine in drinking water at a concentration of 40 p.p.m. for 5 weeks. One week later, the rats were fed diet containing clofibrate at concentrations of of 0,0.1, 0.25, 0.5, and 1% for 19 weeks. Hepatic tumors greater than 1 mm were counted. The doses of 0.1% and 0.25% clofibrate markedly enchanced the incidence of hepatic tumors, whereas 0.5% clofibrate had no effect and 1% clofibrate markedly inhibited hepatocarcinogenesis. It is clearly demonstrated in the present experiments that the lower doses of clofibrate (0.1% and 0.25%) promote hepatocarcinogenesis. The higher doses of clofibrate (0.5% and 1%) depress weight gain by lowering the intake of food. This lowered food intake might contribute to inhibition of hepatocarcinogenesis.

Animals↗
PubMed1982

In vitro measurement of resistance to phalloidin and gamma-glutamyltransferase of carcinogen-induced preneoplastic hepatocytes of rats.

Male inbred F344 rats weighing about 150 g were fed continuously a diet containing 0.02% N-2-fluorenylacetamide for 14-15 weeks. The presumptively preneoplastic hepatocytes were transferred to an in vitro system after dispersion by a collagenase-perfusion technique. Sensitivity to phalloidin in terms of formation of cytoplasmic blebs on the cell surface was less in the presumptively preneoplastic hepatocytes than in normal hepatocytes. Among the presumptively preneoplastic hepatocytes, the gamma-glutamyltransferase (GGT)-positive cells were less sensitive to phalloidin than GGT-negative cells, indicating a greater contribution to the decrease in the sensitivity to phalloidin of the presumptively preneoplastic cells.

2-Acetylaminofluorene↗
PubMed1982

Matrical inclusions of peroxisomes induced by clofibrate in preneoplastic hepatocytes of rats fed 3'-methyl-4-dimethyl-aminoazobenzene.

The response of peroxisomes to clofibrate in preneoplastic hepatocytes of rats fed 3'-methyl-4-dimethylaminoazobenzene was examined histochemically (using the 3,3'-diaminobenzidine reaction) and electron microscopically. Morphometrical examinations revealed that the number of peroxisomes correlated well with the intensity of the histochemical reaction. Preneoplastic hepatocytes which responded to clofibrate with a marked proliferation of peroxisomes showed no matrical inclusions or merely matrical plates in very low incidence in the proliferated peroxisomes. The cells that exhibited a moderate proliferation of peroxisomes showed formation of peroxisomal matrical inclusions in high incidence. The inclusions were matrical plates and tubules showing the same fine structures as those found in 2-acetylaminofluorene carcinogenesis. These peroxisomal inclusions were absent in the cells which responded to clofibrate with no or only a slight increase in the number of peroxisomes. It is suggested that these varieties of peroxisomal changes might reflect the progress of preneoplastic phases of the cells.

Animals↗
PubMed1982

Primary culture of preneoplastic hepatocytes from rats treated with 2-acetylaminofluorene and clofibrate: relationship between resistance to dimethylnitrosamine and responsiveness of peroxisomes.

Hepatocytes of 2-acetylaminofluorene-induced hyperplastic nodules of rats treated with clofibrate were transferred to primary culture after dispersion by a collagenase perfusion technique. After 48-hr treatment with dimethylnitrosamine (DMN), the resistance to the agent of the cells forming rod-shaped peroxisomes was examined. Catalase activity of the DMN-resistant cells was also determined. At concentrations of 10(-3)M and 10(-4)M DMN, the resistant cell population of hepatocytes with rod-shaped peroxisomes was larger than that of the cells without abnormal peroxisomes. On the other hand, the catalase activity of the attached cells that remained after DMN treatment decreased as the concentration of DMN was increased. The cells showing a stronger induction of the enzyme activity were found to be more sensitive to the cytotoxicity of DMN and they became detached from the culture dishes.

2-Acetylaminofluorene↗
PubMed1982

Hepatocytes with extraperoxisomal catalase in rats fed 3'-methyl-4-dimethylaminoazobenzene.

Histochemical and cytochemical studies were done to further characterize the preneoplastic hepatocytes with extraperoxisomal catalase (EPC-cells) that were found in the livers of rats fed 3'-methyl-4-dimethylaminoazobenzene. Catalase activity was demonstrated cytochemically to be localized in nuclear matrices, hyaloplasm, and peroxisomal matrices of EPC-cells. It is suggested that an impairment of peroxisome formation is involved in the altered intracellular distribution of catalase. Administration of clofibrate increased the catalase activity in EPC-cells. To examine the preneoplastic nature of EPC-cells, activities of glucose-6-phosphatase (G6Pase) and gamma-glutamyl transpeptidase (GGT) were examined, since changes in the activities of these enzymes have been used as markers of putative preneoplastic cells. In the present study, neither weak G6Pase activity nor positive GGT activity was considered to be a consistent feature of EPC-cells. However, available evidence suggests that EPC-cells are one of the carcinogen-induced cell populations with altered phenotypes.

Animals↗
PubMed1981

Dose-dependent enhancing effect of phenobarbital on hepatocarcinogenesis initiated by diethylnitrosamine in the rat.

Sequential feeding of various dose levels of phenobarbital (PB) after diethylnitrosamine (DENA) administration revealed that the enhancing effect of PB on hepatocarcinogenesis was dose-dependent. The highest dose level of PB, 0.2% in the diet, greatly enhanced the formation of tumors larger than 5mm in diameter. Tumors obtained in the 0.2% PB feeding group were more numerous and larger in size than those in th 0.01, 0.05, and 0.1% PB feeding groups. although it took longer, the enhancing effect of 0.01% PB feeding was evident when DENA had been administered for 3 weeks, while the same dose level of PB clearly enhanced hepatocarcinogenesis when the carcinogen had been given for 5 weeks.

Animals↗
PubMed1981

Estimation of resistance to dimethylnitrosamine of normal hepatocytes, hyperplastic nodule cells and hepatoma cells of rats in primary culture.

Normal hepatocytes, hyperplastic nodule cells and hepatoma cells of rats induced by 2-acetylaminofluorene treatment were transferred to primary culture. After exposure of the cells to dimethylnitrosamine (DMN) at concentrations of 10(-2) M, 10(-3) M, and 10(-4) M for 48 hr, the attached cells which remained on the dishes in a flattened shape were counted. Resistance to DMN was expressed as the percentage of the attached cells relative to the control without DMN treatment. The percentages increased in the order of normal hepatocytes, hyperplastic nodule cells and hepatoma cells.

Animals↗
PubMed1981

Effect of bolandiol dipropionate (anabiol), an anabolic hormone, on diethylnitrosamine-induced hepatocarcinogenesis in rat.

The effect of bolandiol dipropionate (Anabiol), an anabolic steroid hormone, on hepatocarcinogenesis was investigated in rats. Anabiol was injected at a dose of 5 mg into the thigh muscle at intervals of 2 weeks, simultaneously with or subsequently to the 4-week administration of diethylnitrosamine (DEN). The average number of tumors larger than 3 mm in diameter per rat in the subsequently treated group at 25 weeks after commencement of DEN was significantly increased and the number of tumors larger than 5 mm in diameter per rat in the simultaneously treated group was significantly increased, when compared with that in the group given DEN alone. Thus, the enhancing effect of Anabiol on hepatocarcinogenesis was evident in terms of tumor size, regardless of whether the hormone was given simultaneously with or subsequently to the carcinogen.

Animals↗
PubMed1980

Variation in courtship sounds among three geographical strains of Drosophila mercatorum.

Sound recordings of courtship in Drosophila mercatorum were analyzed with an oscilloscope. Sounds in this species consist of two kinds of pulses, referred to as the A and B sounds, respectively. These differ from each other in their oscilloscope pattern and in the behavior accompanying them. A comparative study of three strains from widely separated geographical regions (New York, El Salvador, and Hawaii) revealed significant differences among strains in the interpulse interval (ipi) of the A sound. The ipi of the B sound increased as it proceeded for New York and Hawaii males but not for males from El Salvador. These characteristics may influence mating success in interstrain crosses. The present results suggest that the first steps toward divergence in the nature of the sound are quantitative; this may affect the response threshold of the female. Genetic systems responsible for female receptivity may have been independently developed in the two sexes.

Animal Communication↗