Biomedical subjects

S Sugie

Publications and source records attributed to S Sugie.

At least 55 records · Page 3Linked to original sources

PubMed1993

Effect of restricted caloric intake on the development of the azoxymethane-induced glutathione S-transferase placental form positive hepatocellular foci in male F344 rats.

The modifying effect of 30% caloric restriction on the occurrence of azoxymethane (AOM)-induced glutathione S-transferase placental form (GST-P) positive hepatocellular foci was investigated in male F344 rats. Starting at 5 weeks of age, groups of animals were fed ad libitum a high-fat (23.5%) semipurified diet. At 7 weeks of age, all animals except the vehicle-treated groups were s.c. injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). Four days after the second injection, groups of animals were continued on high-fat diet and fed ad libitum (ad libitum group) whereas other groups were restricted to 70% of total calories (calorie-restricted group) consumed by the ad libitum group, but received the same amounts of fiber, vitamins and minerals. Thirty-two weeks after AOM injections, all animals were necropsied and livers were sectioned and stained for GST-P by a immunohistochemical technique for quantitative analysis of enzyme altered foci of the liver. Comparing AOM treated groups. The density and the unit area of enzyme altered foci were significantly lower in the calorie-restricted group (3.84 +/- 1.55/cm2, 7.96 +/- 5.43%) than in the ad libitum group (10.14 +/- 3.62/cm2, 28.11 +/- 12.33%). The size of foci was also reduced in the calorie-restricted group (17.15 x 10(-3) mm2 vs. 32.36 x 10(-3) mm2). The incidence and density of hepatocellular foci in rats fed calorie restricted diet were significantly lower than those in rats fed ad libitum, comparing vehicle-treated groups. These results indicate that calorie restriction inhibited the occurrence of both of spontaneous and AOM induced GST-P positive foci in rats.

Animals↗

PubMed1993

Effect of varying proportions of dietary menhaden and corn oil on experimental rat mammary tumor promotion.

Dose-related effects of long-chain highly unsaturated n-3 fatty acids on the development of N-nitrosomethylurea (NMU)-induced rat mammary tumors were assessed in female F344 rats. Four test groups (36 rats/group) were fed the following high-fat (HF) diets (23% fat, w/w): Group 1, 18% menhaden oil (MO) and 5% corn oil (CO); Group 2, 11% MO and 11.8% CO; Group 3, 5% MO and 18% CO; Group 4, CO alone. A fifth group, serving as an internal control, was fed a low-fat diet containing 5% CO alone. Experimental diets were begun after initiation with NMU, and the experiment was terminated 31 wk later. Total tumor numbers in the five groups were 28, 16, 32, 26 and 11, respectively, indicating that the promotion phase of NMU-induced carcinogenesis was significantly suppressed only when equal parts of CO and MO (Group 2) were fed or when CO alone was fed at 5% (w/w). At high (Group 1) or low (Group 3) levels of MO, tumor numbers were indistinguishable from the HF CO group (Group 4). The same pattern was observed when assessed in terms of cumulative tumor incidence and multiplicity. However, when expressed in terms of final tumor incidence, dietary MO did not suppress tumor promotion in a statistically significant fashion at any concentration. Animals fed MO gained weight at the same rate as those fed CO, indicating that the presence of MO in the diet did not result in food avoidance behavior. Measurement of total serum cholesterol indicated an inverse trend with respect to the MO content of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1993

Inhibitory effect of the non-steroidal anti-inflammatory drugs, indomethacin and piroxicam on 2-acetylaminofluorene-induced hepatocarcinogenesis in male ACI/N rats.

The modifying effects of the non-steroidal anti-inflammatory drugs, indomethacin (IMC) and piroxicam (PC) on hepatocarcinogenesis induced by 2-acetylaminofluorene (AAF) were investigated in male ACI/N rats. Rats were divided into 6 groups: group 1 was fed a diet containing 200 ppm AAF for 16 weeks, starting at 6 weeks of age; group 2 was fed an AAF together with 130 ppm PC-containing diet; group 3 received an AAF diet and IMC (10 ppm) in their drinking water; group 4 was fed a PC diet alone; group 5 was given IMC alone; and group 6 served as controls. The PC diet, or the drinking water containing IMC, was given to the rats starting at 5 weeks of age until 1 week after the carcinogen exposure. At termination of the experiment (week 36), the incidences of iron-excluding altered liver cell foci (24.2 +/- 5.2/cm2) and liver cell tumors (1/10, 10%), and the tumor multiplicity (0.10/rat) in rats of group 2 were significantly smaller than those of group 1 (foci incidence, 42.6 +/- 6.7/cm2; tumor incidence, 10/10, 100%; and multiplicity, 4.00/rat) (P < 0.05). Similarly, the incidence of iron-excluding hepatocellular foci (27.4 < 1.2/cm2) and liver cell tumors (1/10, 10%) and the tumor multiplicity (0.10/rat) in rats of group 3 were significantly lower than those of group 1 (P < 0.05). There were no liver cell lesions (foci and neoplasms) in rats of groups 4, 5 and 6. Thus, PC and IMC inhibited the hepatocarcinogenesis induced by AAF when administered concurrently with the carcinogen and the results may indicate possible involvement of altered arachidonic metabolism in the initiation phase of AAF-induced liver carcinogenesis.

2-Acetylaminofluorene↗

PubMed1993

Modifying effects of benzyl isothiocyanate and benzyl thiocyanate on DNA synthesis in primary cultures of rat hepatocytes.

The effects of benzyl isothiocyanate (BITC) and benzyl thiocyanate (BTC) on two types of DNA synthesis were examined in hepatocyte primary cultures (HPC). Male F344 rats were fed BITC- or BTC-containing diets at a concentration of 400 p.p.m. Using hepatocytes isolated from these rats, DNA repair was measured by unscheduled DNA synthesis (UDS) for some genotoxic carcinogens, e.g. 2-acetylaminofluorene (AAF), methylazoxymethanol (MAM) acetate, 9,10-dimethyl-1,2-benzanthracene (DMBA) and diethylnitrosamine (DEN), and compared with that in the hepatocytes from rats without BITC or BTC treatment. Replicative DNA synthesis (RDS) was also evaluated in the hepatocytes of rats with or without thiocyanate treatment. Both BITC and BTC reduced UDS elicited by these carcinogens. The level of RDS in the hepatocytes of rats exposed to BITC or BTC was markedly lower than in the cells of rats without BITC or BTC exposure. These results indicate that in vivo exposure to BITC and BTC suppressed carcinogen-induced genotoxicity and cell proliferative activity and suggest that this assay may prove useful in detecting chemopreventive agents for cancer and in investigating the properties of carcinogenesis modifiers.

Animals↗

PubMed1993

Inhibitory effects of benzyl isothiocyanate and benzyl thiocyanate on diethylnitrosamine-induced hepatocarcinogenesis in rats.

The effects of two aromatic thiocyanates, benzyl isothiocyanate (BITC) and benzyl thiocyanate (BTC), on diethylnitrosamine (DEN)-induced hepatocarcinogenesis were examined in rats. A total of 108 male ACI/N rats, 5 weeks old, were divided into 6 groups (18 rats in each). Group 1 was given a single i.p. injection of DEN (200 mg/kg body weight) one week after the start of the experiment and then kept on the basal diet until the end of the experiment (1 year). Groups 2 and 3 were treated with DEN and received dietary BITC (100 ppm) or BTC (100 ppm), respectively, throughout the experimental duration. Groups 4 and 5 were not given the carcinogen and were fed the diet containing BITC or BTC, respectively. Group 6 was kept on the basal diet alone and served as a control. Liver neoplasms were seen in Groups 1, 2 and 3. Incidence and average number of liver neoplasms in Group 2 were significantly smaller than in Group 1 (P < 0.0005 and P < 0.001, respectively). The incidence of liver neoplasms in Group 3 was slightly lower than in Group 1, although the difference was not statistically significant. The numbers of glutathione S-transferase placental form (GST-P)-positive foci in Group 2 and gamma-glutamyltranspeptidase (GGT)-positive foci in Groups 2 and 3 were significantly smaller than those in Group 1 (P < 0.001). The average and unit areas of GST-P- or GGT-positive foci in Group 2 or 3 were also significantly smaller than those in Group 1 (P < 0.05). These results suggest that BITC and BTC are chemopreventive agents for DEN-induced liver tumorigenesis.

Animals↗

PubMed1993

Synergistic effect of radiation on colon carcinogenesis induced by methylazoxymethanol acetate in ACI/N rats.

The effect on colon and liver carcinogenicity in rats of a single X-irradiation exposure given either before or after methylazoxymethanol (MAM) acetate was studied in ACI/N rats of both sexes. A single dose of X-irradiation (3 Gy) was administered either 3 months before or after three weekly s.c. injections of MAM acetate (25 mg/kg body weight). At 365 days after the start, the incidence and multiplicity of MAM acetate-induced intestinal tumors were enhanced by X-irradiation either prior to or after the MAM acetate treatment. In addition, X-irradiation before MAM acetate increased the incidence of hepatocellular foci in either sex. In females, X-irradiation either before or after MAM acetate exposure decreased intestinal tumorigenesis. These findings suggest an apparent synergism of these agents in intestinal carcinogenesis of male rats.

Animals↗

PubMed1992

Inhibitory effect of 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, a novel synthesized retinoid, on azoxymethane-induced intestinal carcinogenesis in rats.

Modifying effects of 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, a novel synthesized retinoid (KYN-54), on intestinal carcinogenesis were examined in a rat model using azoxymethane (AOM). A total of ninety male F344 rats, 6 weeks old, were divided into 4 groups. Group 1 (20 rats) was fed a diet containing KYN-54 at a concentration of 0.02% for 3 weeks, during which time 2 s.c. injections of azoxymethane (15 mg/kg) were applied and then kept on a basal diet until the end of the experiment (1 year). Group 2 (30 rats) was given azoxymethane as in group 1 and fed the basal diet throughout, without synthetic retinoid exposure. Group 3 (20 rats) was administered KYN-54 at the commencement of the experiment, but not given the carcinogen. Group 4 (20 rats) received a basal diet alone throughout the experiment and served as a control. Intestinal tumors were seen in groups 1 and 2, their incidence and average number in group 1 (74%, 1.07 +/- 0.87) being significantly less than in group 2 (39%, 0.56 +/- 0.78) (P < 0.02 and P < 0.05, respectively). These results suggest that the synthetic retinoid might be a promising chemopreventive agent for intestinal neoplasia.

4-Butyrolactone↗

PubMed1992

A rare case of serous cystadenocarcinoma of the pancreas.

Serous cystadenocarcinoma of the pancreas, a rare disease, developed in a 63-year-old Japanese woman. Pathologic examinations of the pancreatic tumor at the subtotal pancreatectomy showed it to be serous cystadenoma with focal atypical lesions. Three years after the operation, however, metastatic liver nodules were found, and the histologic characteristics of these lesions were quite similar to those of the pancreatic neoplasm. Both primary and metastatic tumors were composed of multiple cysts separated by fibrous septa. The epithelium of cysts was cuboidal and had clear cytoplasm, which had positive results for periodic acid-Schiff (PAS) and negative results for PAS with diastase, Alcian blue, and mucicarmine. To the knowledge of the authors, serous cystic neoplasms of the pancreas have been uniformly benign in biologic behavior. Recently, however, serous cystadenocarcinoma of the pancreas has been reported as a new entity. The current case is the second reported case and might support the existence of serous cystadenocarcinoma of the pancreas.

Cystadenocarcinoma↗

PubMed1992

Effect of voluntary exercise on azoxymethane-induced hepatocarcinogenesis in male F344 rats.

The effect of voluntary exercise on azoxymethane-induced hepatocarcinogenesis was investigated in male F344 rats. Beginning at 5 weeks of age, all animals were divided into two groups (sedentary and exercise) and fed AIN-76A semipurified diet ad libitum. At 7 weeks of age, animals were given azoxymethane (AOM) s.c. at a dose level of 15 mg/kg of body weight, once weekly for 2 weeks. Four days after the second dose of AOM, all animals in the exercise group were housed in individual wheel-cage units and the animals in the sedentary group were housed in plastic cages. The experiment was terminated at 38 weeks post-AOM treatment. Body weights of animals in the exercise and sedentary groups were comparable. Immunohistochemical staining of glutathione S-transferase placental form (GST-P) was performed in the liver and measured GST-P positive foci. Density (number of GST-P positive foci/cm2 area of liver section), average area of foci and unit area of foci were significantly inhibited in the exercise group, although the incidence of neoplastic nodules and GST-P positive foci were unaffected by the exercise. Thus, energy expenditure due to exercise may reduce hepatocarcinogenesis in a laboratory animal model.

Animals↗

PubMed1992

Effect of magnesium hydroxide on methylazoxymethanol acetate-induced epithelial proliferation in the large bowels of rats.

The effect of magnesium hydroxide on the epithelial proliferation of the large bowel was examined using rats given methylazoxymethanol (MAM) acetate. Dietary administration of magnesium hydroxide at 250, 500, 1000 or 2000 ppm. for 1, 3 or 5 weeks did not influence the cell cycle of the cryptal cells of the large bowel. However, the exposure to magnesium hydroxide under these conditions lowered the bromodeoxyuridine labeling index of the cells of the large bowel of the rats which had been initiated by MAM acetate (25 mg/kg, 3 times). The decrease in labeling index was more apparent in the proximal segment than in the distal segment. Such an inhibitory effect on the DNA synthesis of the epithelial cells by magnesium hydroxide may be related to the suppressive action of the trace element on the carcinogen-induced large bowel carcinogenesis.

Animals↗

PubMed1992

Cell kinetic analysis of the mucosal epithelium and assay of ornithine decarboxylase activity during the process of 1-hydroxyanthraquinone-induced large bowel carcinogenesis in rats.

Cell kinetics and activity of ornithine decarboxylase (ODC) were studied during the process of 1-hydroxyanthraquinone (1-HA)-induced intestinal carcinogenesis in rats. Starting at 6 weeks of age, a total of 37 male ACI/N rats were divided into two groups and treated as follows: group I (18 rats) received diet containing 1% 1-HA for 12 months; group II (19 rats) was given the basal diet alone. Sub-groups of 5-7 rats were sequentially killed at 4, 8 and 12 months for evaluation of the length, cell numbers and 5-bromo-2'-deoxyuridine (BrDU) labeling indices of large bowel crypts together with ODC activity. All kinetic and ODC data indicated increased DNA synthesis and proliferation at all time points. Morphological observation of the intestines also revealed melanosis, crypt abscesses and erosion, becoming more pronounced with length of exposure to the anthraquinone. The data thus suggest that cell proliferation in the crypts of the cecum or colon is important for 1-HA-induced intestinal carcinogenesis.

Animals↗

PubMed1992

Modifying effects of fungal and herb metabolites on azoxymethane-induced intestinal carcinogenesis in rats.

Modifying effects of a fungal product, flavoglaucin, and four plant-derived chemicals, shikonin, gingerol, oleanolic acid and paeoniflorin, on intestinal carcinogenesis were examined in a rat model using azoxymethane (AOM). A total of 280 male F344 rats, 6 weeks old, were divided into 12 groups. Group 1 (30 rats) was given two subcutaneous injections of 15 mg/kg of AOM at the start of the experiment. Groups 2 (30 rats), 3 (20 rats), 4 (20 rats), 5 (30 rats) and 6 (30 rats) received a test chemical (flavoglaucin, shikonin, gingerol, oleanolic acid or paeoniflorin, respectively) in the diet at a concentration of 0.02% for 3 weeks, during which time AOM was applied, and then kept on basal diet until the end of experiment (one year). Groups 7-11 (each 20 rats) were given a test chemical corresponding to Groups 2-6, respectively. Group 12 (20 rats) served as a control. The incidence and average number of intestinal tumors in Group 2 (47%, 0.57 +/- 0.68) were significantly less than in Group 1 (74%, 1.07 +/- 0.87) (P < 0.05, respectively). Multiplicity of intestinal neoplasms of Group 3 (0.55 +/- 0.60) or 4 (0.47 +/- 0.51) was also significantly smaller than that of Group 1 (P < 0.05 and P < 0.01, respectively). These results suggest that flavoglaucin, shikonin and gingerol might be promising chemopreventive agents for intestinal neoplasia.

Animals↗

PubMed1992

Carcinogenicity examination of 1-nitropyrene oxides and related chemicals: lack of their tumorigenic effects in a newborn mice assay.

Carcinogenicity of 1-nitropyrene (NP) oxides (1-NP 4, 5-oxide and 1-NP 9, 10-oxide) and related chemicals (1-NP and 1-nitro-6-hydroxypyrene) was examined in the newborn mouse model by i.p. administration at 1, 8, 15 days after birth (each chemical was given at a total dose of 700 nmol per mouse). Low incidences of hepatocellular neoplasms were recognized in male mice exposed to either of these chemicals. However, the incidences were not significantly different from those of animals given solvent alone or of non-treatment. Lymphoma was infrequently seen in female mice given some of tested chemicals. The incidences were also not significantly different from those of mice with the solvent alone or of the controls. The results suggest that although these aromatic hydrocarbons exert genotoxicity or mutagenicity, they may not be potent carcinogens, or the assay with use of newborn mice may be insufficient to monitor carcinogenicity of such chemicals.

Adenoma↗

PubMed1991

Fine-needle aspiration cytology of xanthogranulomatous pyelonephritis.

Fine-needle aspiration cytology of xanthogranulomatous pyelonephritis in a fifty-seven-year-old Japanese woman is reported. Foamy cells and cells showing a gland-like pattern originating from degenerative renal tubules were found in the aspirated smears. Multinucleated giant cells and cells with pale yellowish cytoplasm were seen in the imprint smears at operation. These findings were diagnostic for xanthogranulomatous pyelonephritis. The cytologic diagnostic differences among xanthogranulomatous pyelonephritis, well-differentiated renal cell carcinoma, and renal oncocytoma are also described.

Biopsy, Needle↗

PubMed1991

Genotoxicity of pyrene oxide and 1-nitropyrene oxides in hepatocyte primary culture/DNA repair test.

The genotoxicity of a pyrene oxide, 1-nitropyrene (NP) oxides and other related compounds was examined in the hepatocyte primary culture (HPC)/DNA repair test. Pyrene 4,5-oxide and both 1-NP-4,5-oxide and 1-NP-9,10-oxide elicited clearly positive responses of DNA repair. In this assay, 1-NP itself was weakly positive. However, other related chemicals such as pyrene, 1-nitro-3-hydroxypyrene, 1-nitro-6-hydroxypyrene, and 1-nitro-8-hydroxypyrene did not generate positive responses.

Animals↗

PubMed1991

Effect of dietary benzylselenocyanate on azoxymethane-induced colon carcinogenesis in male F344 rats.

The effect of dietary benzylselenocyanate (BSC) and its analogue, benzylthiocyanate (BTC), and sodium selenite during the initiation and postinitiation phases of azoxymethane (AOM)-induced intestinal carcinogenesis was studied in male F344 rats. Animals intended for initiation study were fed the high-fat (23.5% corn oil) diets containing 25, 50, and 100 ppm BSC (10, 20, and 40 ppm selenium, respectively) and 100 ppm BTC and 4 ppm selenium (as sodium selenite in drinking water); those intended for postinitiation study were fed the high-fat control diet. Two weeks later, all animals were injected subcutaneously with AOM (15 mg/kg body wt) once weekly for two weeks. Three days after the last AOM injection, animals in the initiation and postinitiation studies were transferred respectively to the high-fat diet and high-fat diets containing BSC and BTC and sodium selenite in drinking water. This regimen was continued until 36 weeks post-AOM injection. BSC inhibited the small intestinal and colon adenocarcinoma incidence and multiplicity of colon adenocarcinomas when fed during the postinitiation phase. Sodium selenite inhibited the incidence and multiplicity of colon adenocarcinomas only during the postinitiation phase. BTC had no inhibitory effect when fed during the initiation and postinitiation phases. The colonic mucosal ornithine decarboxylase activity was significantly inhibited by the administration of all three compounds, BSC (78%), BTC (62%), and sodium selenite (44%). It is concluded that the BSC has an inhibitory effect on the intestinal carcinogenesis in animals fed the high-fat diet.

Analysis of Variance↗

PubMed1991

Enhancing effect of ethanol or saké on methylazoxymethanol acetate-initiated large bowel carcinogenesis in ACI/N rats.

Effects of ethanol or saké on intestinal carcinogenesis by methylazoxymethanol (MAM) acetate were examined in two experiments. In the first experiment, 39 male ACI/N rats were given two weekly intraperitoneal injections of MAM acetate (25 mg/kg body wt) and divided into two groups, with Group 1 being given 10% ethanol and Group 2 being given distilled water. The incidence of colonic cancer in Group 1 (15/17, 88%) was higher than in Group 2 (9/16, 56%, p = 0.040). Differences in the incidences of rectosigmoidal colonic neoplasms were even more marked (59% vs. 19%, p = 0.019) and their proportion of the total number of large intestinal neoplasms was greater in Group 1 (36%) than in Group 2 (15%, p = 0.046). In the second experiment, 97 female ACI/N rats were divided into 6 groups, with the animals of Groups 1-5 being given MAM acetate (2 times, 25 mg/kg body wt). Rats in Group 6 received saline. The rats received isocaloric drinks: Group 1, saké; Group 2, 50% saké; Groups 3 and 6, 15% ethanol; Group 4, 7.5% ethanol; and Group 5, nonalcoholic water. Incidences of rectosigmoidal colonic neoplasms in Groups 1, 2, and 3 (53%, 46%, and 50%) tended to be higher than in Group 5 (38%). Their proportions of the total number of large intestinal neoplasms in Groups 1 (68%) and 2 (67%) were slightly greater than in Group 5 (45%). The results suggest an enhancing effect of ethanol or saké on rectosigmoidal colonic carcinogenesis.

Alcoholic Beverages↗

PubMed1991

Inhibitory effect of the non-steroidal anti-inflammatory drug, indomethacin on the naturally occurring carcinogen, 1-hydroxyanthraquinone in male ACI/N rats.

The effect of the non-steroidal anti-inflammatory drug indomethacin on 1-hydroxyanthraquinone (1-HA)-induced carcinogenesis was investigated in male ACI/N rats. Animals were fed the diet containing 1.5% 1-HA and simultaneously given indomethacin solution (16 p.p.m.) as drinking water for 48 weeks. The incidences of large bowel neoplasms (adenomas and adenocarcinomas) and forestomach (papillomas) in rats given 1-HA and indomethacin (large intestinal tumors: 0/14, 0%; forestomach tumors: 2/14, 14%) were significantly lower than those in rats given 1-HA alone (large intestinal tumors: 12/27, 44%; forestomach tumors: 14/27, 52%) (P = 0.002 and P = 0.01 respectively). Liver cell adenomas were developed in a rat given 1-HA and no liver tumors in rats treated with 1-HA and indomethacin. Altered liver cell foci were present in rats given 1-HA alone (18/27, 67%) and those given 1-HA and indomethacin (8/14, 57%), but no significant difference in the incidence between the two groups was found. Untreated animals and rats given indomethacin alone had no neoplasms in the large bowel, forestomach and liver. Thus, the non-steroidal anti-inflammatory drug indomethacin significantly inhibited carcinogenesis induced by the naturally occurring carcinogen, 1-HA.

Adenocarcinoma↗