Biomedical subjects

T Imazawa

Publications and source records attributed to T Imazawa.

At least 73 records · Page 4Linked to original sources

PubMed1994

[A 13-week subchronic toxicity study of bisphenol A in B6C3F1 mice].

A 13-week subchronic toxicity study of bisphenol A (BPA) was performed in male and female B6C3F1 mice at dose levels of 0, 0.2, 0.5, 1.0, 2.0 and 4.0% in the diet, to facilitate dose selection for a subsequent carcinogenicity study. Mice were randomly allocated to 6 groups, each consisting of 10 males and 10 females. Two 0.2% group males and two 4.0% group females died during the experimental period. Suppression of body weight gain and increase in food consumption were observed in males and females of the 4.0% groups. Hematological examination revealed decrease in number of erythrocytes, volume of hemoglobin and value of hematocrit in males and females of the groups receiving 1.0% or above, and an increase in number of platelets in males of 4.0% group. Decrease in number of erythrocytes and hematocrit value was also noticed in females of 0.5% group. Histopathologically, cystic dilatation, degeneration or regeneration of renal tublues were found in males and females of 1.0% or higher groups, multinucleated hepatocytes were increased in mice of both sexes treated with any dose of BPA, and fibrous osteodystrophy was observed in males and females of the 4.0% groups. Based on the results of the present study, it was concluded that the maximum tolerance dose (MTD) of BPA is 0.2% in diet, because the dose level of 0.5% proved to exert significant hematological toxicity.

Administration, Oral↗

PubMed1993

Carcinogenicity study of 1,1-bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane in B6C3F1 mice.

1,1-Bis(tert-butylperoxy)-3.3.5-trimethylcyclohexane (BBTC) is widely used in the manufacture of rubber. The present carcinogenicity study in B6C3F1 mice was carried out in order to assess its potential to induce tumours. BBTC was administered at dietary levels of 0 (control), 0.25 and 0.5% for 78 wk; these dose levels were selected on the basis of a subchronic toxicity study, in which body weights were depressed to less than 90% of the control group values and swelling of hepatocytes was histologically evident in animals fed 1% BBTC or more in the diet. Neoplasms were found in all groups, including the control group, but there were no significant differences between groups of either sex in mortality, tumour incidences or tumour distribution. All tumours were considered to be spontaneous because of the similarity to background data for B6C3F1 mice. This study thus provides no evidence of carcinogenicity of BBTC in B6C3F1 mice.

Anemia↗

PubMed1993

Effects of hickory smoke condensate on gastric carcinogenesis in Wistar rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

Short-term assays in vivo have suggested that hickory smoke condensate (HSC), a food flavouring, might have tumour-initiating and/or promoting activities in the glandular stomach of the rat. In the present study, the modifying effects of HSC on glandular stomach carcinogenesis after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride (MNNG salt) were investigated in male Wistar rats. Animals were given MNNG solution (100 ppm) as drinking water and simultaneously fed the diet supplemented with 5% sodium chloride for 8 wk. Matched negative controls received neither MNNG nor sodium chloride. Rats were then fed a basal diet and given HSC solution (1 or 3%) or tap water for the following 32 wk. During the experimental period, treatment with MNNG salt and administration of HSC both brought about growth retardation although the final body weight of rats was comparable between groups. Only two rats treated with MNNG salt followed by 1% HSC developed adenocarcinoma of the stomach. HSC treatment appeared to increase the number of rats with preneoplastic hyperplasias and/or adenocarcinomas in both the fundic and pyloric mucosa, although not to a statistically significant extent. HSC administration significantly increased malondialdehyde levels in the urine and gastric mucosa, the former in a dose-dependent manner. The results suggest that HSC has little, if any, promoting effect on two-stage glandular stomach carcinogenesis in rats when given during the post-initiation phase. However, the tumour co-initiating effects of HSC require further clarification.

Adenocarcinoma↗

PubMed1993

Relationship between bisacodyl-induced urolithiasis and rat urinary bladder tumorigenesis.

Dietary supplementation with bisacodyl at concentrations ranging from 1 to 0.3% was found to induce both calculi and epithelial proliferative lesions, including a transitional-cell carcinoma, in the urinary bladder of F344/DuCrj rats. In order to clarify the relationship between the bisacodyl-associated urinary bladder calculi and the development of proliferative lesions in the urinary bladder, male and female rats were administered bisacodyl-diets at concentrations of 0.3, 0.1, and 0.03% for 32 wk. Both sexes of animals treated with bisacodyl suffered from diarrhea throughout the experimental period. Epithelial proliferative lesions and calculus formation were observed only in the urinary bladder of male rats given the 0.3% bisacodyl diet. Proliferative lesions and increases of bromouracil deoxyriboside (BUdR) labeling indices were found only in the urinary bladder epithelium of rats with calculi, the severity of the former correlating with the calculus weight and being most marked in the dome areas, which are susceptible to physical stimulation. These findings indicate a close relationship between the development of proliferative lesions and the existence of calculi in the urinary bladder, and suggest that bisacodyl-induced proliferative lesions are not caused directly by bisacodyl per se but are secondary to calculus formation.

Administration, Oral↗

PubMed1993

Temporal dissociation between cell proliferation and eosinophilic foci development in the exocrine pancreas of rats initiated with 4-hydroxyaminoquinoline 1-oxide and administered soybean trypsin inhibitor.

Male Sprague-Dawley rats received a single i.v. injection of 4-hydroxyaminoquinoline 1-oxide (HAQO) 7 mg/kg body weight or vehicle alone, and starting 7 days thereafter, were then fed basal diet with or without a 5% soybean trypsin inhibitor (SBTI) supplement. Subgroups were sequentially killed after 2, 4, 7, 14, 30, 60 and 100 days on this regimen, in each case 1 h after injection of bromodeoxyuridine (BrdU). In the HAQO/SBTI and SBTI alone groups, 2 days after the SBTI treatment the labeling indices of acinar cells were increased approximately 12- and 11-fold respectively, dropping rapidly thereafter and returning to the control value by day 30. The earliest eosinophilic foci were noted in the HAQO/SBTI group 60 days after HAQO initiation, with the component cells demonstrating markedly increased labeling indices in contrast to the completely normalized levels observed in the surrounding exocrine tissue. On the other hand, eosinophilic foci were scarcely induced in the HAQO or SBTI alone group throughout the experiment. These results thus indicate a clear temporal dissociation between initial proliferation in parenchymal pancreatic tissue caused by SBTI and subsequent development of eosinophilic foci in rats initiated with HAQO.

4-Hydroxyaminoquinoline-1-oxide↗

PubMed1993

An experimental model for anaplastic astrocytomas and glioblastoma using adult F344 rats and N-methyl-N-nitrosourea.

An experimental model for induction of gliomas corresponding to human anaplastic astrocytomas and glioblastomas is reported. Eleven week old F344 and ACI rats were given 100 or 200 p.p.m. N-methyl-N-nitrosourea (MNU) solution as their drinking water for 42 weeks. Gliomas were induced at very high incidences (82.5-92.5%) in each group. Induced gliomas showed apparent evidence of morphologic malignancy by an analysis based on diagnostic criteria of human astrocytomas. All of the gliomas from the killed animals were classified histologically into subtypes according to the classification scheme used in the diagnosis of human gliomas. The majority of macrotumors more than 1 mm in diameter in both strains were diagnosed as anaplastic astrocytomas and glioblastomas. Immunohistochemically, tumor cells in these tumors were almost negative for glial fibrillary acidic protein, while ultrastructurally neoplastic astrocytes contained glial filaments. A strain difference was observed in the ratio of histological subtypes of macrotumors. In F344 rats, astrocytic tumors diagnosed as anaplastic astrocytomas and glioblastomas of an astrocytic type formed the majority, whereas glioblastomas of mixed oligo-astrocytic type predominated in ACI rats. The results indicate that MNU-administration to adult F344 rats may provide a suitable experimental model for gliomas which occur in adult humans.

Animals↗

PubMed1993

Spontaneous histiocytic sarcoma with possible origin from the bone marrow and lymph node in Donryu and F-344 rats.

Ninety-five male and 96 female Donryu rats reared up to 120 wk of age and 244 male and 243 female F-344 rats used as untreated controls in 5 carcinogenicity studies were examined histopathologically to clarify the primary site of histiocytic sarcoma. Histiocytic sarcoma in Donryu rats was observed in 5 of 95 (5.3%) males and 4 of 96 (4.2%) females. In F-344 rats, 4 of 244 (1.6%) males and 3 of 243 (1.2%) females had the neoplasms. Histologically, sarcomas consisting of large pleomorphic histiocytic cells were seen in the bone marrow, liver, lymph node, spleen, and lung. Among 16 sarcomas observed, 15 had neoplastic lesions in the bone marrow, and 1 F-344 rat had the lesions only in the lymph nodes. Eleven (6 F-344 rats and 5 Donryu rats) of the 15 cases had the lesions in the liver, and 4 Donryu rats had no lesions in the liver but lesions in the lymph node and/or spleen, except for 1 case where the sarcoma occurred only in the bone marrow. Among the 11 cases with the lesions both in the liver and bone marrow, neoplastic lesions were found also in the lymph node, spleen, and/or lung, but the severity of neoplastic proliferation of these organs was not so marked as that in the bone marrow except for 2 cases. Although histiocytic sarcomas in rats are considered to originate from the liver, peritoneum, or subcutis, the present results strongly suggest that some histiocytic sarcomas in Donryu and F-344 rats may also originate from the bone marrow and lymph nodes.

Animals↗

PubMed1993

[Effects of cyclophosphamide on spontaneous testicular and pancreatic lesions in WBN/Kob rats].

This study was undertaken to investigate the effects of cyclophosphamide (CP) on spontaneous pancreatitis and testicular atrophy of WBN/Kob rats. CP was given daily in drinking water to groups of 20 male 6-week-old WBN/Kob rats at doses of 0 (control), 1.25 or 2.5 mg/kg for 20 weeks. The final body weight in the 2.5 mg/kg CP group was significantly lower than that in the control group. There were no significant differences in blood glucose levels and weights of the pancreas and testis between groups. On histopathological examinations, pancreatitis and testicular atrophy were noted in each group. However, the incidence of pancreatitis characterized by inflammatory cell infiltration and fibrosis in the 2.5 mg/kg CP group was significantly decreased as compared to the control group. In contrast, testicular atrophy was more severe in the 2.5 mg/kg CP group than in the control group. Thus the results demonstrated that CP has inhibitory effects on the development of pancreatitis and enhancing effects on the development of testicular atrophy in WBN/Kob rats.

Administration, Oral↗

PubMed1992

Effects of caffeine, nicotine, ethanol and sodium selenite on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine.

The modulating effects of caffeine, nicotine, ethanol and sodium selenite on development of N-nitrosobis(2-oxopropyl)-amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given s.c. injections of BOP (10 mg/kg body weight) or saline alone once a week for 3 weeks and then administered 2000 p.p.m. caffeine, 25 p.p.m. nicotine, 20% ethanol or 4 p.p.m. sodium selenite in their drinking water for the next 37 weeks. Control animals were given tap water alone after BOP initiation. Only the BOP-treated groups developed pancreatic adenocarcinomas and dysplasias. The multiplicity of pancreatic carcinomas was significantly higher (P less than 0.05) in animals receiving caffeine than in the controls. In addition, caffeine treatment slightly increased the incidence of carcinomas. Nicotine and ethanol also showed tendencies to enhance pancreatic carcinogenesis, although there were statistically no significant differences regarding lesion development. In contrast, sodium selenite administration was associated with a tendency for a decrease in the number of carcinomas and dysplasias. Thus, among these chemicals of obvious significance to human life-style, caffeine enhanced the development of pancreatic tumors when administered during the post-initiation phase in this hamster model.

Animals↗

PubMed1992

Induction of pancreatic tumors in male Syrian golden hamsters by intraperitoneal N-methyl-N-nitrosourea injection.

The carcinogenic effects of N-methyl-N-nitrosourea (MNU) in male Syrian golden hamsters were investigated. After single i.p. administration of MNU at doses of 50 mg/kg or 10 mg/kg, or after five fractionated i.p. injections to make a total dose of 50 mg/kg body weight (10 mg x 5), histopathological examinations were performed at the end of 40th week of the experiment. Neoplastic changes were observed in various organs, and lesions in the pancreas, forestomach, and adrenal gland were predominant. In the pancreas, three tumor types were observed: ductal adenocarcinomas, acinar cell carcinomas, and islet cell carcinomas. The incidences of pancreatic ductal carcinomas were 56, 27, and 0% in the single 50-mg, fractionated 50-mg, and single 10-mg groups, respectively. Two islet carcinomas were observed in the single 50-mg group, and an islet carcinoma and an acinar cell carcinoma were also observed in the fractionated 50-mg group. Several miscellaneous neoplastic lesions, including squamous cell papillomas/carcinomas in the forestomach, cortical adenomas in the adrenal glands, and a seminoma in the testis were also observed. These results indicate MNU to be a multipotent carcinogen with the pancreas as a target organ in the Syrian golden hamster under this experimental condition. The observed high induction rate for pancreatic ductal carcinoma suggests that this MNU protocol is a useful candidate model for experimental pancreatic ductal carcinogenesis.

Animals↗

PubMed1992

Modifying effects of soybean trypsin inhibitor on development of eosinophilic nodules and basophilic foci in the exocrine pancreas of male Sprague-Dawley rats treated with 4-hydroxyaminoquinoline 1-oxide.

Administration of 4-hydroxyaminoquinoline 1-oxide (HAQO) to rats results in development of 2 types of pancreatic acinar lesions, namely eosinophilic nodules and basophilic foci. To cast light on the biological character of these lesions, 5-week-old male Sprague-Dawley rats were given a single intravenous injection of HAQO at a dose of 7 mg/kg and, thereafter, fed soybean trypsin inhibitor (SBTI) at dose levels of 10% and 5%. At week 57, all rats were killed for pathological examination of pancreatic tissue. The incidence of eosinophilic nodules was significantly higher in the HAQO/SBTI group than in the HAQO-alone group, whereas the basophilic acinar foci were observed to occur less frequently and to be smaller in the HAQO/SBTI-treated animals. Administration of SBTI is known to increase the blood level of cholecystokinin, a trophic factor for pancreatic acinar cells. Thus, the present findings suggest that long-term elevation of this endocrine factor can affect the two types of pancreatic acinar lesions in essentially different ways, namely enhancing development of eosinophilic nodules, while suppressing the occurrence of basophilic foci.

4-Hydroxyaminoquinoline-1-oxide↗

PubMed1992

[Studies on cell proliferation activities in acute toxic lesions in the liver and pancreas of hamsters treated with N-nitrosobis(2-oxopropyl)amine].

Histopathology and cell proliferation activities in acute toxic lesions in the liver and pancreas of female Syrian hamsters given a S.C. injection of N-nitrosobis(2-oxopropyl)amine (BOP) at a dose of 100 mg/kg, were investigated. Histologically, at one day after administration, hypertrophy and focal necrosis of the hepatocytes were observed, whereas no remarkable changes were seen in the pancreas. At 7 days after administration, when diffuse hypertrophy, vacuolation and necrosis of the hepatocytes, and atypical hyperplasia of the bile duct were seen in the liver, hyperplasia of the pancreatic duct and focal necrosis and vacuolation of the acinar cells were noticed in the pancreas. Immunohistochemistry for both 5-bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) revealed remarkable increases of cell proliferation activities in the target cells for BOP toxicity, especially at 7 days after BOP treatment. Meanwhile, the number per nucleus of silver-stained proteins related to nucleolar organizer regions (AgNOR) was significantly increased in the target cells at both 1 and 7 days after BOP treatment. Thus, in the present study, it was suggested that acute toxic changes in the liver of hamsters treated with BOP precedes those in the pancreas. The speculation that AgNOR may be an indicator recognizing earlier alterations on acute BOP toxicity remains to be examined.

Animals↗

PubMed1991

Dose-dependent enhancing effects of quinacrine on induction of preneoplastic glutathione S-transferase placental form positive liver cell foci in male F344 rats.

Dose-dependent modifying effects of quinacrine on induction of preneoplastic liver cell foci were investigated in male F344 rats. Six week old animals were injected i.p. with N-nitrosodiethylamine (DEN) at a dose of 200 mg/kg, and starting 2 weeks later, rats were given quinacrine at dietary levels of 20, 100 and 500 p.p.m. for 6 weeks. Groups without either DEN or quinacrine treatment were used as controls. At week 3 following DEN administration, all animals were subjected to two-thirds partial hepatectomy, and after killing the animals at week 8, development of preneoplastic liver cell foci was investigated using the glutathione S-transferase placental form (GST-P) as a marker. The numbers and unit areas of GST-P-positive foci per cm2 were significantly increased in the DEN/quinacrine (500 p.p.m.) group as compared to DEN-alone group values. An increase in number was also evident in the 100 p.p.m. but not the 20 p.p.m. treated group, no lesions being induced by quinacrine alone (500 p.p.m.). Electron microscopic study confirmed that quinacrine dose-dependently induces lipidosis in hepatocytes, i.e. markedly myeloid lamellar cytoplasmic inclusion bodies were observed. The results thus demonstrated that quinacrine treatment enhances GST-P-positive liver cell foci development in a dose-dependent way, this effect presumably being related to the induction of lipidosis.

Animals↗

PubMed1991

Inhibitory effects of soybean trypsin inhibitor on induction of pancreatic neoplastic lesions in hamsters by N-nitrosobis(2-oxopropyl)amine.

The effects of simultaneous soybean trypsin inhibitor (SBTI) treatment on initiation of pancreatic carcinogenesis by N-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Female Syrian golden hamsters were given five weekly s.c. injections of BOP at a dose of 10 mg/kg while being administered a diet containing 5% SBTI for 5 weeks (BOP + SBTI group). Two other groups of 30 animals each received the s.c. injections of BOP or the 5% SBTI diet for the same period, alone (BOP and SBTI groups respectively). Total numbers of pancreatic dysplastic lesions in hamsters of the BOP+SBTI group were significantly decreased as compared to the BOP group values, though the incidences of pancreatic adenocarcinomas were not significantly different. Atrophic changes were, however, more severe in the BOP group than in the BOP+SBTI group pancreatic exocrine tissue, showing that treatment with SBTI was effective for protection of acinar cells from carcinogen toxicity.

Adenocarcinoma↗

PubMed1991

[Twenty-eight-day repeated dose toxicity test of p-phenetidine in F344 rats].

A twenty-eight-day repeated dose toxicity test of p-phenetidine was carried out in male and female F344 rats at dose levels of 160, 40, 10 or 0 mg/kg/day. Thirty animals of both sexes were divided into 6 groups of equal number. All groups were treated daily by i.g. administration for 28 days, two extra groups of animals at dose levels of 160 and 0 mg/kg being used for investigation of recovery over 14 days. Hematological and urinary examinations revealed decrease in erythrocytes and increased serum reticulocytes and urinary urobilinogen in the 160 and 40 mg/kg groups of both sexes, and methemoglobinemia occurred in the 160 mg/kg group. Increase in spleen weight was noted in the 160 and 40 mg/kg groups. On histopathological examination, hemosiderosis, increased extramedullary hemopoiesis, congestion of the spleen and myeloid hyperplasia of the bone marrow were observed in the 160 and 40 mg/kg groups of both sexes. Repair of these lesions occurred within 14 days after the cessation of administration. Based on these findings, a no-observed-effect level for p-phenetidine would be concluded 10 mg/kg/day.

Animals↗

PubMed1991

[Subchronic oral toxicity study of stevioside in F344 rats].

A 13-week subchronic oral toxicity study of stevioside was carried out in F344 rats at dose levels of 0, 0.31, 0.62, 1.25, 2.5 and 5% in diet, to determine appropriate dose levels for a 2-year carcinogenicity study. The rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Between the control and treated groups, there were no differences in body weight gain during the administration period and in food consumption in the later period of the study. LDH on biochemical investigation and single cell necrosis in the liver revealed by histopathological examination were increased in all male treated groups. These were not considered specific changes, because of the lack of any clear dose response, the relatively low severity and the limitation to males. Other parameters that were found to demonstrate significant differences on hematological and biochemical investigations were of minor toxicological significance. From these results, a concentration of 5% in diet was concluded to be a suitable maximum tolerable dose of stevioside for a 2-year carcinogenicity study in rats.

Administration, Oral↗

PubMed1991

[Ultrastructural study of the blood-testis barrier in rat by the lanthanum method].

Ultrastructural changes of the testes in 35-week-old WBN/Kob rats were investigated using the lanthanum-tracer method. Tissues were cut and fixed with a solution containing 1% lanthanum and 2% glutaraldehyde in a 0.1 M sodium cacodylate buffer at pH 7.8 and with a solution of 2% osmium and 1% lanthanum in a 0.1 M sodium cacodylate buffer. Ultrathin sections of epoxy resin-embedded specimens were stained with uranyl acetate and lead citrate and observed into a JEM-100CXS JEOL transmission electron microscope. The remnants of each testis were fixed in Bouin's fixative, and observed light-microscopically, where almost all seminiferous tubules in all of the six testes were found to be severely atrophied. Electron microscopically, lanthanum pigments were limited in the Sertoli cell tight junctions of the seminiferous tubules even in the severely atrophied tubules. In conclusion, it is unlikely that the testicular atrophy in WBN/Kob rats is attributable to dysfunction of the blood-testis barrier.

Animals↗

PubMed1990

[Lectin reactivity in the kidney of newborn rat compared to adult rat].

The distribution of binding sites for 13 lectins with different specificities was studied in adult and new-born rat kidney tissue by staining paraffin sections with the ABC method. Various segments of the uriniferous tubule in both rats showed differential affinity for lectins. None of these lectins showed any reactivity with the immature developmental components of kidney like S-shaped bodies and mesonephric blastema. In the new-born rat kidney, the reactivity of 4 lectins (DBA, PNA, SBA and WGA) on the proximal tubules was very weak compared with the adult rat. Seven lectins (RCA-I, BSL-I, WGA, UEA-I, PHA-E, PSA, LCA), which stained the glomerulus of adult rats, failed to react with glomerular turf in new-born rat kidneys. On the contrary, 4 lectins (RCA-I, WGA, UEA-I and PHA-E) out of these 7 lectins stained the surface of podocyte in the new-born kidney. Colloidal iron stained glomerular turf in adult rats also showed less reactivity in immature glomerulus. These results suggested that changes in lectin binding reactivity are associated with the development and the differentiation of the rat kidney.

Animals↗