Biomedical subjects

S Tamano

Publications and source records attributed to S Tamano.

At least 91 records · Page 5Linked to original sources

PubMed1988

L-ascorbic acid amplification of second-stage bladder carcinogenesis promotion by NaHCO3.

The dose dependence of NaHCO3 promotion of urinary bladder carcinogenesis and the effects of additional L-ascorbic acid (AsA) administration were investigated subsequent to initiation. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then, starting 3 days after cessation of carcinogen treatment, received basal diet containing NaHCO3 at levels of 0, 0.375, 0.75, 1.5, and 3.0% with or without a 5% AsA supplement for 32 weeks. NaHCO3 dose-dependently increased the incidence and numbers of urinary bladder carcinomas in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. 5% AsA, while itself exerting no promoting effect, amplified the enhancing influence of NaHCO3 on induction of urinary bladder carcinomas. The same dose-dependent elevation of urinary pH and Na+ concentration was associated with NaHCO3 treatment with or without AsA. NaHCO3 significantly increased DNA synthesis in the urinary bladder epithelium and the additional treatment with AsA was associated with a significant further elevation. Thus, increased urinary pH and Na+ concentrations appear to play important roles in NaHCO3 promotion and AsA amplified this promotion. NaHCO3 treatment, with or without AsA, induced cellular proliferation, although it is unclear whether this is an essential factor.

Animals↗

PubMed1988

The role of urinary pH and sodium ion concentration in the promotion stage of two-stage carcinogenesis of the rat urinary bladder.

The promoting activities of NaHCO3 and NaCl in two-stage urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated. Male F344 rats were given 0.05% BBN in their drinking water for 4 weeks and then treated with basal diet containing either 3% NaHCO3, 1% NaCl or no added chemical for 32 weeks. NaHCO3 significantly increased the induction of neoplastic and preneoplastic lesions of the urinary bladder, whereas NaCl did not. NaHCO3 produced elevation of urinary pH and urinary Na+ concentration. NaCl increased urinary Na+ concentration without the elevation of urinary pH. In an additional experiment, DNA synthesis in the urinary bladder epithelium was significantly increased in the groups given 3% NaHCO3, 5% sodium L-ascorbate and 1% NaCl. These results confirm that urinary components, increase in urinary pH and Na+ concentration play an important role in the promotion of urinary bladder carcinogenesis in rats.

Animals↗

PubMed1988

Spontaneous tumors in aging (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice.

Spontaneous tumors in untreated (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice used as controls in carcinogenicity tests were recorded. In both sexes, the development of spontaneous tumors was age-related. In 244 male mice, the most common tumors were hyperplastic nodules of the liver, hepatocellular carcinomas, malignant lymphomas/leukemias, lung adenomas, and adenocarcinomas. In 246 female mice, the most common tumors were malignant lymphomas/leukemias, pituitary adenomas, neoplastic nodules of the liver, hepatocellular carcinomas, and lung adenomas. Hepatocellular carcinomas metastasized in 20.3% of the animals with these tumors. Few other tumors except malignant lymphomas and leukemias metastasized. Various tumors of other organs and/or tissues were found at low incidences.

Age Factors↗

PubMed1987

Promotion by L-ascorbic acid of urinary bladder carcinogenesis in rats under conditions of increased urinary K ion concentration and pH.

Dietary administration of 5% L-ascorbic acid plus 3% K2CO3 to male F344 rats clearly enhanced the development of preneoplastic and neoplastic lesions of the urinary bladder initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. Promotion of carcinogenesis by L-ascorbic acid and K2CO3 was associated with changes in urinary parameters: elevation of pH, increased K+ concentration, and increase in total ascorbic acid.

Animals↗

PubMed1987

Combined chronic toxicity and carcinogenicity studies of morpholine oleic acid salt in B6C3F1 mice.

Morpholine oleic acid salt (MOAS) was administered to groups of 50 male and 50 female B6C3F1 mice in the drinking-water at levels of 0, 0.25 and 1.0%. Both sexes given 1.0% MOAS and females given 0.25% showed growth retardation. Significant increases in blood-urea nitrogen concentrations were only observed in the 1.0% male group. The incidence of squamous-cell hyperplasia of the forestomach epithelium was significantly higher in the males given 1.0% than in the controls. The male mice given 0.25% MOAS had a significantly reduced incidence of hepatocellular carcinoma in comparison with the control group and this trend was indicated also in the 1.0% group. This experiment did not demonstrate any carcinogenic effect of MOAS in mice at levels up to 1.0% in the drinking-water.

Animals↗

PubMed1987

Modification by alpha-tocopherol, propyl gallate and tertiary butylhydroquinone of urinary bladder carcinogenesis in Fischer 344 rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The promoting activity of 3 antioxidants, alpha-tocopherol (alpha-TP), propyl gallate (PG) and tertiary butylhydroquinone (TBHQ) in urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male F344 rats was examined. Rats, 6-week-old, were treated with 0.05% BBN in the drinking water for 4 weeks and then administered 1.50, 0.75 or 0.38% alpha-TP, 1.0% PG or 2.0% TBHQ in the diet for 32 weeks. The urinary bladder of all animals was examined histologically after the total 36 experimental weeks. The incidence of papillary or nodular hyperplasia (PN hyperplasia) of the urinary bladder was significantly higher in the rats treated with BBN followed by 2.0% dietary TBHQ that in controls initiated with 0.05% BBN followed by control diet. This result indicates that TBHQ has weak promoting activity in urinary bladder carcinogenesis. alpha-TP and PG did not demonstrate a promoting effect for urinary bladder lesions.

Animals↗

PubMed1987

13-week subchronic toxicity study with morpholine oleic acid salt administered to B6C3F1 mice.

The effect of subchronic administration of morpholine oleic acid salt (MOAS) was studied in B6C3F1 mice. The dose levels of MOAS used were 0%, 0.15%, 0.3%, 0.6%, 1.25%, and 2.5% in drinking water. Reduced weight gains were noted in both sexes in the 2.5% group as compared to controls, but reductions were not significant. Water consumption values showed a dose-related tendency for a decrease in both females and males. Urine analysis showed significant elevation of specific gravity in the males in the 0.6%, 1.25%, and 2.5% groups and the females in the 1.25% and 2.5% groups. Significant elevation of plasma urea nitrogen was observed in males of the 1.25% and 2.5% groups and in females of the 0.6%, 1.25%, and 2.5% groups. The relative weight of the kidneys showed a dose-dependent increase that was statistically significant for the 1.25% and 2.5% MOAS groups in both sexes. Except for cloudy swelling of the proximal tubules of the kidneys in mice on the 2.5% regimen, no treatment-related histopathological alterations were observed in organs of either sex.

Animals↗

PubMed1987

Aging and urinary bladder carcinogenesis induced in rats by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of age on induction of carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine [(BBN) CAS: 3817-11-6] in the urinary bladder epithelium was examined in 130 male and 130 female F344 rats. Rats of both sexes 6, 52, and 98 weeks old were given 0.025% BBN in their drinking water for 20 weeks. Then approximately half the rats were sacrificed, while the rest were maintained without further treatment for 10 weeks. Examination of the rats revealed an age-related increase in the induction of urinary bladder carcinoma, although the total intakes of BBN and urinary excretions of its proximate carcinogen were not age related. Rats treated with BBN at 98 weeks of age developed more squamous cell carcinomas and invasive carcinomas than the 2 younger groups. This study demonstrated an increased risk of urinary bladder carcinogenesis with age in animals.

Aging↗

PubMed1986

Changes in the urine and scanning electron microscopically observed appearance of the rat bladder following treatment with tumor promoters.

Urine of rats treated with promoters of urinary bladder carcinogenesis was analyzed during weeks 8 to 24 of administration. The sodium salts of several chemicals, including ascorbic acid, erythorbic acid, acid saccharin and o-phenylphenol increased the urinary pH and sodium ion concentration of the urine. In contrast, treatment with sodium hippurate did not cause elevation of urinary pH although it increased the sodium ion concentration in the urine. Butylated hydroxyanisole, butylated hydroxytoluene (BHT), and ethoxyquin did not affect the urinary pH or any electrolytes except for an increase of phosphorus in the urine of rats given BHT or ethoxyquin. Scanning electron microscopic examination showed that epithelial cells of the urinary bladder of rats given promoters of urinary bladder carcinogenesis had pleomorphic microvilli, short, uniform microvilli, and ropy or leafy microridges on their surfaces. Thus, for the class of promoters including the sodium salts of weak to moderate acids, the elevation of urinary pH and the increase of sodium ion concentration accompany the promoting activity, whereas these changes do not occur following administration of the antioxidant class of bladder tumor promoters.

Animals↗

PubMed1986

Sequential changes of the forestomach of F344 rats, Syrian golden hamsters, and B6C3F1 mice treated with butylated hydroxyanisole.

Butylated hydroxyanisole (BHA) was given to F344 rats, Syrian golden hamsters and B6C3F1 mice at 2 doses for up to 104 weeks. The two doses were 2.0% and 1.0% for rats and hamsters, and 1.0% and 0.5% for mice. Animals were sacrificed sequentially at 8-week intervals from week 8 to week 104, and the carcinogenic effects of BHA on the forestomach were examined histopathologically. Papillomas and carcinomas were found in rats, hamsters and mice. In rats, papillomas first appeared in week 8 in the group given the higher level of BHA and in week 56 in that given the lower level. The first carcinoma was observed in week 48 in rats given the high level, while no carcinoma was observed in rats given the lower level. In hamsters, papillomas appeared in week 8 in both BHA-treated groups, and in both groups, the incidence of papillomas was much higher than in BHA-treated rats. Squamous cell carcinomas were observed in 4 hamsters (10.0%) among those that survived more than 64 weeks on treatment with the higher level of BHA and in 4 (7.3%) among those treated with the lower level. In mice, papillomas were induced by BHA in both BHA-treated groups after more than 88 weeks. Although the incidence was not statistically significant, carcinoma was also seen in mice, suggesting that BHA may also be carcinogenic to mouse forestomach.

Animals↗

PubMed1986

Dose response in butylated hydroxyanisole induction of forestomach carcinogenesis in F344 rats.

Groups of 50 6-week-old male F344 rats were given a powdered diet containing 0, 0.125, 0.25, 0.5, 1, or 2% butylated hydroxyanisole [(BHA) CAS: 25013-16-5] for 104 weeks. The highest dose--2% BHA--induced significant increase in the incidence of squamous cell carcinoma of the forestomach. Papillomas of the forestomach developed in 20 and 100% of the rats given diets containing 1 and 2% BHA, respectively. The incidence of epithelial hyperplasia of the forestomach increased with the increased BHA doses, to 100% incidence at the highest dose. Thus the incidences of proliferative and neoplastic lesions of the forestomach were dose dependent.

Animals↗

PubMed1986

[Evaluation of the carcinogenic risk of environmental chemicals].

Many carcinogens have been detected in our environment, and chemicals which have been shown to induce cancers in experimental animals have been largely eliminated. However, there are still many chemicals which have not been studied in rodent carcinogenicity tests. In this paper, we review the evaluation of carcinogenic risk of environmental chemicals to humans. Carcinogenic risk to humans is evaluated primarily in three different phases: carcinogenicity studies in animal experiments, in vitro short-term screening studies, and finally human epidemiological studies. There are 30 chemicals, processes or industries which have been subject to these three phases and determined to be carcinogenic to humans by the International Agency for Research on Cancer (IARC). Carcinogenic risk of chemicals should be evaluated quantitatively by their threshold doses, TD50 and virtually safe dose (VSD). Furthermore, the target organ of the carcinogen should also be taken into account, which has been emphasized by the demonstration of carcinogenicity of BHA in the forestomach of rats. Summational, synergistic, antagonistic and inhibitory effects of chemicals should also be discussed. It is important to establish a guideline for detecting and eliminating environmental carcinogens in order to prevent cancer in humans.

Animals↗

PubMed1986

Roles of urinary sodium ion concentration and pH in promotion by ascorbic acid of urinary bladder carcinogenesis in rats.

Since the sodium salt of ascorbic acid (AA) promoted two-stage urinary bladder carcinogenesis in rats, whereas AA itself did not, the roles of the urinary sodium ion concentration and pH on urinary bladder carcinogenesis were investigated. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then treated with basal diet containing 5% AA plus 3% sodium bicarbonate (NaHCO3), 5% AA, 3% NaHCO3 or 5% sodium L-ascorbate (SA), 5% SA plus 1% ammonium chloride (NH4Cl) or 1% NH4Cl, or no added chemical for 32 weeks. NaHCO3 significantly increased the induction of neoplastic and preneoplastic lesions of the urinary bladder. Like SA, AA plus NaHCO3 induced high incidences of neoplastic and preneoplastic lesions of the urinary bladder, whereas AA alone did not. NH4Cl reduced the promoting activity of SA in urinary bladder carcinogenesis. These results suggest important roles for urinary sodium ion concentration and pH in modulating urinary bladder carcinogenesis. Moreover, AA was found to act as a copromoter under conditions of increased urinary pH and sodium ion concentration.

Animals↗

PubMed1985

Inhibitory potential of acetaminophen and o-, m-, p- aminophenols for development of gamma-glutamyltranspeptidase-positive liver cell foci in rats pretreated with diethylnitrosamine.

The inhibitory potential of treatment with acetaminophen (AAP) and 3 different isometric forms of monoaminophenols (o-, m-, p-AP) for the development of gamma-glutamyltranspeptidase-positive (gamma-GT+) liver cell foci was examined in an in vivo short-term assay system. Rats were initially given a single intraperitoneal injection of diethylnitrosamine (DEN) and fed test compounds from week 2 until they were killed at week 6, all rats being subjected to two-thirds partial hepatectomy at week 3. All 4 compounds exerted obvious inhibition of the development of gamma-GT foci with both number and area (mm2) being reduced. AAP proved the most potent agent whereas dose-related inhibitory potential was observed within the 2 doses of p-AP treated.

Acetaminophen↗

PubMed1985

Subchronic toxicity study of sodium o-phenylphenate in mice.

A 13-week subchronic oral toxicity study of sodium o-phenylphenate (SOPP) was conducted in B6C3F1 mice. Body weight gain was significantly depressed in 1.0 and 2.0% SOPP-treated males and in both sexes treated with 4.0%. Urinalysis showed an increase in pH and a decrease of specific gravity in the 4.0% group of both sexes. Relative liver weights of both sexes receiving 1.0, 2.0 and 4.0% SOPP were significantly greater than those of the controls. No treatment-related histopathologic findings were noted. On scanning electron microscopic (SEM) examination, the bladder epithelium of mice given 2.0% SOPP appeared normal at any time periods investigated. This study showed that while 4.0% SOPP was very toxic to both sexes, 2.0% SOPP did not cause statistically significant changes in organ weights.

Animals↗

PubMed1985

Comparative effects of carcinogens on the induction of placental glutathione S-transferase-positive liver nodules in a short-term assay and of hepatocellular carcinomas in a long-term assay.

The dose-dependent effects of three hepatocarcinogens were investigated by measuring the number and area of glutathione S-transferase placental form (GST-P)-positive foci and nodules appearing in the liver under short-term conditions (Experiment I) and evaluating the incidence of hepatocellular carcinoma after long-term chronic administration (Experiment II). For these purposes, three different doses of 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethy-laminoazobenzene (3'-Me-DAB), and DL-ethionine (ethionine) were given to male F344 rats for 6 weeks after a single injection of diethylnitrosamine (DENA) in Experiment I or for 104 weeks without initiation by DENA in Experiment II. In Experiment I, the induction of GST-P-positive foci and nodules by 2-AAF and 3'-Me-DAB was clearly dose-dependent. In contrast, ethionine showed enhancing effects inducing GST-P-positive foci and nodules only in groups given the highest dose level. Similarly, in Experiment II, induction of hepatocellular carcinomas by 2-AAF and 3'-Me-DAB was clearly dose-dependent, whereas liver neoplasms were only induced by the highest dose level of ethionine. These results indicate that degree of induction of GST-P positive foci and nodules in a short-term in vivo test for liver carcinogens corresponds with the incidences of hepatocellular carcinomas revealed in a long-term in vivo assay.

Animals↗

PubMed1985

Promoting effect of trisodium nitrilotriacetate monohydrate on urinary bladder carcinogenesis in rats.

The promoting effect of trisodium nitrilotriacetate monohydrate (Na3NTA X H2O) on two-stage urinary bladder carcinogenesis in F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at levels of 0.01 and 0.05% was investigated. Administration of 2.0% Na3NTA X H2O significantly increased both the incidence and the number per 10 cm of basement membrane of preneoplastic lesions and papillomas of the urinary bladder in rats pretreated with 0.05% BBN. This result shows that Na3NTA X H2O has weak promoting activity in urinary bladder carcinogenesis.

Acetates↗

PubMed1984

Modification of N-methyl-N-nitrosourea initiated carcinogenesis in the rat by subsequent treatment with antioxidants, phenobarbital and ethinyl estradiol.

The modifying effects of butylated hydroxyanisole (BHA), sodium L-ascorbate (SA), phenobarbital (PB) and ethinyl estradiol (EE) were studied by their administration to F344 rats subsequent to initiation with N-methyl-N-nitrosourea (MNU), a wide-spectrum carcinogen inducing tumors in many organs. Rats were initially given 4 doses of MNU (50 mg/kg) intraperitoneally within a 2-week period and then placed on a diet containing BHA (1%), SA (5%), PB (0.05%) or EE (0.001%) for 23 weeks prior to killing. Since the experiment was based on a whole body concept of carcinogenesis, all major organs were examined histologically and histochemically for any preneoplastic lesions. BHA enhanced forestomach and urinary bladder carcinogenesis as did SA also for the urinary bladder, whereas PB enhanced the induction of gamma-glutamyl transpeptidase positive (gamma-GT+) foci in the liver and also the incidence of thyroid carcinoma and forestomach carcinoma. In contrast, EE inhibited the induction of thyroid tumors, malignant lymphoma or leukemia. Thus these compounds, when given after initiation of many organs by a single carcinogen, exert an influence on the site of tumor development by, as yet unknown, organotropic modifying effects.

Animals↗