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Biomedical subjects

S Tamano

Publications and source records attributed to S Tamano.

At least 73 records · Page 4Linked to original sources
PubMed1991

13-Week oral toxicity study of captafol in F344/DuCrj rats.

Captafol fed at concentrations of 0, 0.075, 0.15, 0.3, and 0.6% to both sexes of F344 rats for 13 weeks produced dose-related decreases in body weight in males and females given 0.15% or higher concentrations. A dose-dependent decrease in urinary pH was observed in males receiving 0.3 or 0.6% and in females given 0.15% or higher concentrations of captafol. The 0.3 and 0.6% doses produced slight increases in leukocyte count and glutamic-pyruvic transaminase activity in females, along with a mild increase in alkaline phosphatase activity in the 0.6% case. The liver- and kidney-to-body weight ratios were increased in both male and female rats. Histopathological changes were observed in the forestomach, liver, and kidney. Squamous cell hyperplasia and edema accompanied by polynuclear leukocyte infiltration and dilation of vessels in the lamina propria were observed in the forestomach of both sexes given 0.15% or higher concentrations. Oval cell proliferation was apparent around Glisson's sheath in the livers of females given 0.3 and 0.6% captafol. Multifocal appearance of karyocytomegaly and tubular cell atypia in the proximal tubules of the kidney was found in the 0.3 and 0.6% groups of both sexes.

Alanine Transaminase↗
PubMed1991

Uracil-induced calculi and carcinogenesis in the urinary bladder of rats treated simultaneously with N-butyl-N-(4-hydroxybutyl)nitrosamine.

Urinary bladder carcinogenicity of uracil and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in combination was investigated in male F344 rats. Two experiments were performed: in the first animals were treated with 3.0, 1.0 and 0.3% uracil in the diet and/or 0.005% BBN in the drinking water for 36 weeks followed by a 4 week period without chemicals, the total observation time being 40 weeks; in the second rats received 3.0% uracil in the diet or 0.05% BBN in the drinking water for 4 weeks. In the first experiment, a markedly high incidence of carcinomas was observed in the urinary bladder with both 3.0% uracil alone (11/15, 73%) and 3.0% uracil plus 0.005% BBN (18/20, 90%) treatments. The multiplicity, i.e. numbers of carcinomas induced per 10 cm of basement membrane, was significantly higher with the latter treatment (P less than 0.05), as were proliferative lesions in the renal pelvis. Stone formation was observed in all 3.0% uracil treatment animals. In the second experiment, prostaglandin E2 levels in bladder tissue of uracil-treated animals proved to be significantly higher than in BBN-treated or untreated animals. Thus, the results clearly indicated that calculi associated with 3.0% uracil ingestion can themselves cause carcinoma development in the urinary bladder, while also acting as a potent co-carcinogen agent for BBN carcinogenesis.

Animals↗
PubMed1991

Induction of invasive carcinomas of the seminal vesicles and coagulating glands of F344 rats by administration of N-methylnitrosourea or N-nitrosobis(2-oxopropyl)amine and followed by testosterone propionate with or without high-fat diet.

The potential modifying effects of testosterone propionate (TP) and high-caloric high-fat diet (20% corn oil, HF) on rat accessory sex gland carcinogenesis were investigated. Male F344 rats were treated five times at 4-week intervals with N-methylnitrosourea (MNU) i.v. or N-nitrosobis(2-oxopropyl)amine (BOP) s.c., each injection following 2 weeks pretreatment with dietary ethinyl estradiol. After completion of this carcinogen administration stage, animal groups received subcutaneous implantation of Silastic tubes filled with 40 mg TP with or without HF for 40 weeks. Carcinomas of the seminal vesicles and/or coagulating glands were induced in 5, 39 and 56% of rats given MNU alone, MNU and TP, and MNU and HF plus TP respectively. No equivalent tumors were found in rats given MNU and HF. In the BOP-treated groups, 11% of animals receiving TP but no HF diet demonstrated seminal vesicle carcinomas and 6% of rats receiving TP plus HF diet had coagulating gland carcinoma. Thus while TP exerted a strong enhancing effect on tumor growth in the seminal vesicles and coagulating glands, high caloric HF did not manifest any significant influence.

Animals↗
PubMed1991

A new colon and mammary carcinogen in cooked food, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is produced during cooking and is mutagenic to bacteria and cultured mammalian cells, was found to induce high incidences of colon and mammary carcinomas in F344 rats when administered at a concentration of 400 p.p.m. in the diet for 52 weeks. Since PhIP is the most abundant of the mutagenic heterocyclic amines in cooked meat and fish, the compound might be related to malignancies of the colon and breast in humans.

Animals↗
PubMed1991

Time- and dose-dependent induction of invasive urinary bladder cancers by N-ethyl-N-(4-hydroxybutyl)nitrosamine in B6C3F1 mice.

A sequential investigation of N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) bladder carcinogenesis was performed in male B6C3F1 mice maintained ad libitum on tap water containing 0.025% EHBN for 4, 12, 20, 28 and 36 weeks. A total of 81 invasive tumors, comprising 55 squamous cell carcinomas (SCCs) (68%), 25 transitional cell carcinomas (TCCs) (31%) and 1 adenocarcinoma (1%) were found. Of these, 23 (22 SCCs and 1 TCC) demonstrated invasion to the prostate, 3 metastasized to the lung, and 2 spread by peritoneal seeding. The anaplastic grade and extent of invasion of the SCCs significantly exceeded those of the TCCs. The results suggested a histogenetic pathway from simple dysplasia through papillary or nodular dysplasia and/or carcinoma in situ to eventual development of invasive carcinomas.

Animals↗
PubMed1990

Bladder epithelial hyperplasia in F344 rats after intravesical instillation of the antitumor chemotherapeutic agents Adriamycin and mitomycin C.

The effects of intravesical instillation of the antineoplastic antibiotics, Adriamycin or mitomycin C, on the urinary bladder epithelium of female F344 rats were evaluated using a combined immunohistochemical and morphological approach. Four weeks treatment with Adriamycin or mitomycin C induced an increase of DNA synthesis and was associated with simple hyperplasia characterized by elevated nuclear cytoplasmic ratios, cytomegaly and pleomorphism. Under the scanning electron microscope (SEM), luminal cell surface alterations such as pleomorphic microvilli were observed. Severity of the lesions was greatest in the Adriamycin group and although treatment of the saline vehicle alone also brought about development of simple hyperplasia, this was very slight and not accompanied by cellular pleomorphism. The present results demonstrated that intravesical instillation of antineoplastic agents can cause a proliferative response and cytotoxicity after only short-term treatment and suggest that this chemotherapy could itself play a possible role in promotion of bladder carcinogenesis or cancer development.

Administration, Intravesical↗
PubMed1990

Lack of modifying effects of p-phenylenediamine on induction of gamma-glutamyl transpeptidase-positive foci in a medium-term bioassay system using F344 rats.

The modifying effects of p-phenylenediamine (p-PD) on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given p-PD at dietary levels of 1000, 330 and 110 parts per million (ppm), or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at 600 ppm as a positive control for 6 weeks. At week 3 following DEN administration, all animals were subjected to partial hepatectomy. Slight retardation of body weight was observed in rats treated with p-PD at all dietary levels. Significant increases in relative liver weight were found in animals treated with 1000 ppm p-PD. Remarkable growth retardation and increased liver weight were found in rats given 3'-Me-DAB. p-PD did not significantly increase the level of gamma-glutamyl transpeptidase (gamma-GT) positive foci observed after DEN initiation. In contrast, 3'-Me-DAB demonstrated marked enhancing activity as evidenced by significantly increased values for gamma-GT positive foci as compared with the controls given DEN alone. The results demonstrate that p-PD does not modify liver carcinogenesis in our in vivo medium-term bioassay system.

Animals↗
PubMed1990

Correlation between medium-term liver bioassay system data and results of long-term testing in rats.

The effects of hepatocarcinogens (ethionine, thioacetamide, phenobarbital), non-hepatocarcinogens [N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)] and a hepatoinhibitor [(butylated hydroxyanisole (BHA)] were compared in medium- and long-term in vivo systems. In experiment I, 2 weeks after a single injection of diethylnitrosamine (DEN) groups of male F344 rats received chemical administration for 6 weeks, combined with partial hepatectomy at week 3 and were killed at the end of week 8. In experiment II, animals were treated in the same manner and then given basal diet and tap water (group 1) or chemical continuously (group 2) until the 2 year timepoint. Numbers and areas of glutathione S-transferase placental form (GST-P)-positive foci developing in the liver under medium-term bioassay conditions (experiment I) were found to closely correlate with eventual hepatocellular carcinoma incidences after continuation of test chemical administration (experiment II). Thus all of the hepatocarcinogens enhanced both the induction of GST-P-positive focal lesions and liver tumors. While non-hepatocarcinogens exerted no such effects, their influence being limited to inducing lesions in their own respective target organs such as urinary bladder cancers in the EHBN case and glandular stomach adenocarcinomas with MNNG, BHA demonstrated inhibition potential in both experiments. The observed correlation between long- and medium-term results strongly indicates the applicability of our medium-term bioassay system for detection of liver carcinogens.

Animals↗
PubMed1990

Carcinogenicity of captafol in F344/DuCrj rats.

Captafol was administered at dietary levels of 0 (control), 750 and 1,500 parts per million (ppm) to groups of 50 male and 50 female F344/DuCrj rats for 104 weeks, and then all animals were maintained without captafol for a further 8 weeks, and killed in week 113. Renal cell carcinoma was found in eight of 50 male rats treated with 1,500 ppm and in one of 50 male rats treated with 750 ppm of captafol. The incidences of renal adenomas, including micro-adenomas, and basophilic altered cell tubules were significantly higher in both sexes treated with captafol than in controls, and the increases were apparently dose-dependent except that of adenomas in females. The incidences of neoplastic and preneoplastic lesions of the kidney in captafol-treated animals were higher in males than in females. Captafol also induced hepatocellular carcinomas in four of 50 female rats in the 1,500 ppm group. The incidences of hyperplastic (neoplastic) nodules and foci of cellular alterations in the liver were also significantly increased in both sexes treated with captafol, the increases being dose-dependent. In conclusion, captafol induced renal cell carcinomas in male rats and hepatocellular carcinomas in female rats.

Adenoma↗
PubMed1990

Promoting effect of the peroxisome proliferator, clofibrate, but not di(2-ethylhexyl)phthalate, on urinary bladder carcinogenesis in F344 rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The modifying potential of clofibrate and di(2-ethylhexyl)phthalate (DEHP) on second stage, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated urinary bladder carcinogenesis was investigated in male F344 rats, using a uracil-accelerated transitional cell proliferation model. Six-week-old animals received 0.05% BBN in their drinking water for 4 weeks and then clofibrate (1.0, 0.5, and 0.25%) and DEHP (1.2, 0.6, and 0.3%) were given during experimental weeks 5-8 and weeks 12-20. Uracil was administered during weeks 9-11 at a dietary level of 3.0%. Control rats were treated with BBN and uracil without peroxisome proliferator. Surviving animals were killed at the end of week 20 of the experiment, when the densities of putative preneoplastic, papillary or nodular (PN) hyperplasias (numbers per 10 cm of basement membrane) were significantly increased in all clofibrate-treated, but not the DEHP groups. The incidences of PN hyperplasia were similar in both treated animals and controls. In a second experiment, rats fed diets containing 1.0% clofibrate or 1.2% DEHP were assessed for levels of DNA synthesis in urinary bladder epithelium by 5-bromo-2-deoxyuridine immunohistochemistry. Numbers of labeled nuclei remained within normal levels, and no proliferative changes were evident. Thus, the present experiments indicated that while clofibrate, but not DEHP, exerts weak enhancing effects on BBN-initiated urinary bladder carcinogenesis in rats this is not associated with increased levels of DNA synthesis in the affected epithelium.

Animals↗
PubMed1989

Proliferative response of renal pelvic epithelium in rats to oral administration of ortho-phenylphenol, sodium ortho-phenylphenate and diphenyl.

Changes in DNA synthesis levels and morphology as observed by scanning electron microscopy (SEM) and light microscopy in rat renal papilla and pelvis following oral administration of ortho-phenylphenol (OPP), sodium ortho-phenylphenate (OPP-Na) and diphenyl, were investigated in F344 rats. OPP and OPP-Na treatment for 4 weeks was associated with elevated DNA synthesis in both renal papilla and pelvis, in addition to distinct morphological cell surface alterations. Sequential light microscope observation revealed induction of renal papillary necrosis from week 4, followed by regeneration hyperplasia at weeks 16 and 24, but no changes in the renal pelvis in the OPP case. OPP-Na not only similarly affected the renal papilla, but also brought about development of hyperplasia in the renal pelvis. No proliferative response of the kidney was apparent in rats fed diphenyl. The present study indicated that the proliferative responses in the renal pelvic epithelium following OPP-Na are similar to those induced by this chemical in the urinary bladder, and that in both cases they are indicative of promoting or carcinogenic potential.

Administration, Oral↗
PubMed1989

Lack of carcinogenicity of magnesium chloride in a long-term feeding study in B6C3F1 mice.

Groups of 50 male and 50 female B6C3F1 mice were given magnesium chloride (MgCl2.6H2O) at dose levels of 0 (control), 0.5 and 2% in the diet for 96 wk, after which all animals received the control diet for 8 wk and were then necropsied. In females of the high-dose group a decrease in body weight was observed. However, survival rates did not differ between the treatment and control groups for males or females. Furthermore, clinical signs and urinary, haematological or serum clinical chemistry parameters showed no treatment-related effects. On histological examination, tumours were mainly found in the skin/subcutis, liver and lymphatic system. However, with the exception of a significant decrease in the incidence of liver tumours among males of the high-dose group, no differences were noted in the tumour incidence between the treated and control animals. Thus, the study described here clearly shows a lack of carcinogenicity of MgCl2.6H2O given to B6C3F1 mice in the diet.

Animals↗
PubMed1989

Participation of urinary Na+, K+, pH, and L-ascorbic acid in the proliferative response of the bladder epithelium after the oral administration of various salts and/or ascorbic acid to rats.

Changes in urinary parameters (particularly electrolyte levels and pH), and DNA synthesis and the morphology of the bladder epithelium were investigated in rats that were fed for 4 or 8 wk on diets containing various Na, K, Mg or Ca carbonate salts, with or without L-ascorbic acid (AsA). [The carbonate salts were fed at a level of 3% in the diet, and AsA or AsA-Na was administered at 5% in the diet. NH4Cl was at 1% in the diet.] The effects of treatment with NH4Cl (used as a urine acidifier), and of combined treatment with sodium ascorbate (AsA-Na) and NH4Cl were also investigated. Urinary pH was significantly elevated in groups given NaHCO3, K2CO3, AsA + NaHCO3, AsA + K2CO3 and AsA-Na, whereas treatment with AsA or NH4Cl alone caused a significant drop in urinary pH. An increase in urinary electrolytes or ascorbic acid was associated with the corresponding dosing regimen. DNA synthesis in the bladder epithelium was increased in groups given NaHCO3, K2CO3, AsA + NaHCO3, AsA + K2CO3 or AsA-Na. Furthermore, all treatments that induced an elevation of DNA synthesis also induced some morphological alterations in the bladder epithelium. The administration of AsA in conjunction with NaHCO3 or K2CO3 induced levels of change greater than those with either salt alone. In contrast, the degree of response in the bladder epithelium of rats given AsA-Na was reduced by the simultaneous administration of NH4Cl. These results suggest that the degree of DNA synthesis and/or morphological alteration in the rat-bladder epithelium after treatment with various bases may depend on changes in urinary concentrations of Na+ or K+ ions and/or pH, and the presence of ascorbic acid in the urine. The results are discussed in relation to the possible promotion by various treatment regimens (salts +/- AsA) of urinary bladder carcinogenesis.

Administration, Oral↗
PubMed1989

Lack of a modifying effect by the diuretic drug furosemide on the development of neoplastic lesions in rat two-stage urinary bladder carcinogenesis.

The effect of the diuretic drug furosemide on two-stage urinary bladder carcinogenesis in F344 rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was investigated with regard to possible promoting activity. BBN was administered at 2 doses, 0.01 or 0.05%, in drinking water for 4 wk, and thereafter furosemide was given by gavage 3 times weekly for 32 wk, 250 mg/kg body weight. Furosemide ingestion induced diuresis with an alkaline, hypotonic urine. No significant difference with regard to incidences of bladder lesions were apparent between furosemide and control groups. The present investigation indicated that neither furosemide nor its related polyuria acted as a promoter in two-stage urinary bladder carcinogenesis.

Animals↗
PubMed1989

Lack of carcinogenicity of quercetin in F344/DuCrj rats.

Quercetin was administered at dietary levels of 0(control), 1.25 and 5.0% to groups of 50 male and 50 female rats for 104 weeks, and then all animals were maintained without quercetin supplement for a further 8 weeks. At 5.0% quercetin, both sexes showed growth retardation throughout the study. There were no treatment-ascribed effects regarding clinical signs, mortality, urinalyses or hematology. Although serum glucose in 5.0% quercetin-treated males was significantly decreased and some relative organ weights in 5.0% groups showed statistically significant increases, these latter changes seemed to be related to the growth retardation. An increased incidence of non-neoplastic hyperplastic polyps in the cecum was noted in the 5.0% males. The incidences of cystic changes and fibroadenomas of the mammary gland, and foci (areas) of hepatocellular alteration in the 5.0% females, and liver bile duct proliferations in the 5.0% males were significantly decreased. No proliferative lesions of the urinary bladder related to treatment with quercetin were found in any rats. The incidences of several other nonneoplastic and neoplastic lesions which demonstrated statistically significant changes appeared to be related to the growth retardation or to be within the normal range, and therefore none was considered to be significant biologically. Thus, the investigation did not demonstrate any clear carcinogenic effect of quercetin on F344 rats at dietary levels of up to 5.0%.

Animals↗
PubMed1989

Lack of modifying effects of 2,2'-[(4-aminophenyl) imino] bisethanol sulfate on induction of preneoplastic gamma-glutamyl transpeptidase-positive foci in a medium-term bioassay system using F344 rats.

The modifying effects of 2,2'-[(4-aminophenyl) imino] bisethanol sulfate (4APE) on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given 4APE at dietary levels of 1,000, 330 and 110 parts per million (ppm), or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at 600 ppm as a positive control for 6 weeks. At week 3 following DEN administration, all animals were subjected to partial hepatectomy. No adverse effects on survival and body weight were seen in rats treated with 4APE, even at the highest dietary levels. Marked growth retardation and significant increase of relative liver weight were found in animals treated with the known hepatocarcinogen 3'-Me-DAB, which demonstrated marked promoting activity as evidenced by significantly increased values for gamma-glutamyl transpeptidase (gamma-GT) positive foci as compared with the controls given DEN alone. In contrast, 4APE did not significantly increase the level of gamma-GT positive foci over that induced by DEN initiation alone. From these results, it is concluded that 4APE does not possess promoting activity for liver carcinogenesis.

Animals↗
PubMed1989

[Modifying effects of beraprost sodium (TRK-100) on N-methyl-N-nitrosourea (MNU) carcinogenesis in F344 rats].

The potential tumor-promoting effects of beraprost sodium (TRK-100), stable analogue of prostacyclin (PGI2), were investigated in rats pretreated with N-methyl-N-nitrosourea (MNU) which is a potent initiator of tumor development in a variety of organ or tissues. Male F344 rats were initially given injections of MNU (20 mg/kg b.w. i.p.) twice a week for 3 weeks, and then administered drinking water containing 6, 2, 0.7 or 0.2 ppm of beraprost sodium for the next 29 weeks. For comparison, positive control groups received N-propyl-N-nitrosourea (PNU), which is a carcinogen in hematopoietic system and small intestine on F344 rat, at the dose of 200, 50 and 12.5 ppm in their drinking water. Appropriate non-treated controls were also included. Numerous tumors were observed in many organs including the hematopoietic system, digestive tract, nervous system, Zymbal's gland (auditory sebaceous glands) and peritoneal mesothelium. However, no tumor-enhancing effects of beraprost sodium were observed. In contrast, the groups treated with PNU demonstrated increased development of tumors in the tongue, forestomach, large intestine and Zymbal's gland. These results thus indicate that beraprost sodium is not capable of modulating the development of MNU-induced tumors.

Animals↗