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K Imaida

Publications and source records attributed to K Imaida.

At least 127 records · Page 7Linked to original sources
PubMed1990

[Early histopathological changes in trachea, bronchus and lung, and changes in lipid peroxidation in hamsters, due to inhaled cigarette smoke].

The main objective of this work was to determine the influence of cigarette smoke exposure on the mechanisms which promote respiratory tumors. And another aim was the accumulation of basic data regarding the effect of cigarette smoke exposure in hamsters in the Hamburg II smoking machine. Male Syrian golden hamsters were caused to inhale cigarette smoke in the Hamburg II smoking machine. The hamsters inhaled cigarette smoke twice a day, for 9 minutes, 5 times a week. The administration period were 1,2,4,8 and 12 weeks. For each inhalation, the rotating disk was fitted with 30 cigarettes. Each puff, 35 ml in volume, was diluted seven times with room air. At the completion of administration, subjects were examined histopathologically, and lung and serum lipid peroxidation levels were also measured. Histopathological examination of the respiratory tract and alveolar epithelium disclosed no cigarette smoke-related hyperplastic lesion in any animal. And in the hamsters which inhaled cigarette smoke, "smoke cells" accumulation were observed in the alveolar space after 8 and 12 weeks exposure. Significant increase in the number of BrdU positive cells were not observed following cigarette smoke exposure, but a tendency for lung malondialdehyde (MDA) levels to increase was evident. On the other hand, serum lipid peroxide (LPO) levels showed a marked decrease in the animals exposed to cigarette smoke for 2,4 and 8 weeks in comparison with the identically handled control animals. But serum LPO levels showed a tendency to increase with cigarette smoking during all experimental periods. The above results suggested that cigarette smoking may cause a change in lipid peroxidation levels such as lung MDA and serum LPO levels.

Animals↗
PubMed1990

[Ultrastructural localization of myelin bodies and acid phosphatase activities in the liver and kidney induced by quinacrine in rats].

Electron microscopic studies were conducted to reveal the ultrastructural aspects of the myelin body and acid phosphatase activity in rats induced by quinacrine, an antimalarial drug. Each of 22 rats in three groups were examined. The first group of control rats was initially given a single i.p. dose (200 mg/kg) of diethylnitrosamine (DEN) only and then fed a CRF-1 basal diet for 8 weeks. The second and third group were treated with DEN or saline, and starting 2 weeks later, were fed a CRF-1 basal diet supplemented with 500 ppm quinacrine for 6 weeks. All animals were subjected to a partial hepatectomy at week 3, and then sacrificed at week 8. Liver and kidney tissues specimens from 2 rats per group were collected for routine electron microscopic study. Furthermore, the activity of acid phosphatase, a key enzyme for lysosomal activity, was also investigated. In this study, tissues were fixed with a solution of 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer. After fixation, tissues were frozen and their 8 microns sections were treated with Gomori's lead nitrate buffer solution, and post-fixed with a 1% osmium solution. After being embedded in Epon 812, ultrathin sections were made. Intracellular myelin bodies were observed in the hepatocytes, interlobular bile duct cells, renal glomerular podocytes and renal tubular cells in the quinacrine treated groups, but not were observed in rats treated with DEN alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1989

Elevated activity of pancreatic type amylase in the urine as an early indicator of pancreatic tumors in hamsters.

Levels of amylase isozymes in the urine and serum of Syrian hamsters during pancreatic carcinogenesis, induced by N-nitrosobis(2-oxopropyl)amine (BOP), were investigated. BOP was injected subcutaneously (sc) into female Syrian golden hamsters at a dose of 10mg/kg once weekly for 6 wk and amylase activities in urine and serum samples were measured every other week from the first treatment of BOP. Although total amylase in the urine showed no remarkable changes, the pancreatic type isozyme demonstrated only very low levels for the first 6 wk and then from wk 8, became elevated showing continuously high levels in all animals thereafter. Animals were sacrificed at wk 10, 14, and 18. Dysplastic lesions of the pancreas developed in all the hamsters investigated. Furthermore, pancreatic adenocarcinomas were also observed in all animals sacrificed at wk 18. Thus, the results suggest that measurement of pancreatic isoamylase in the urine might allow early indication of pancreatic tumor development in hamsters.

Adenocarcinoma↗
PubMed1989

Effects of glyoxal and methylglyoxal administration on gastric carcinogenesis in Wistar rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine.

Glyoxal and methylglyoxal were tested for tumor-promoting potential in a two-stage stomach carcinogenesis model. Male outbred Wistar rats were initially given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/l) along with a 10% sodium chloride dietary supplement for 8 weeks. Thereafter, they were returned to basal diet and maintained on drinking water containing no addition or either 0.5% glyoxal or 0.25% methylglyoxal for 32 weeks and then killed for necropsy and histological examination at week 40. Glyoxal treatment significantly increased the incidence of adenocarcinomas in the pylorus of the glandular stomach of rats pretreated with MNNG and sodium chloride. Furthermore, although methylglyoxal did not enhance the development of adenocarcinomas, the incidence of hyperplasias in the pylorus was significantly increased. The results indicate that glyoxal exerts tumor promoting activity on rat glandular stomach carcinogenesis and that methylglyoxal might also have promoting potential.

Aldehydes↗
PubMed1989

Sequential analysis of quinoline-induced hepatic hemangioendothelioma development in rats.

The effect of duration of quinoline treatment on the induction of hepatic hemangioendotheliomas was examined. Groups of male Wistar rats were given 0.25% quinoline in the diet for 4, 8, 12, 16 or 20 weeks and sequentially killed at these time points. Hemangioendotheliomas were only induced in the livers of rats given quinoline for more than 12 weeks and the incidences of small foci of dysplastic endothelial cells and tumors at week 20 did not differ between the 12-, 16- and 20-week-treated groups. Quantitative analysis of the liver sections at week 20 revealed increased relative area occupied by sinusoidal space even after only 4-week exposures. Parenchymal hyperplastic nodules were observed only in one rat each of the 16- and 20-week-treated groups. The present study indicates that dysplastic endothelial foci may develop into hemangioendotheliomas irrespective of whether the carcinogenic stimulus is continued.

Animals↗
PubMed1989

Sodium o-phenylphenate (OPP-Na) promotes skin carcinogenesis in CD-1 female mice initiated with 7,12-dimethylbenz[a]anthracene.

Sodium o-phenylphenate (OPP-Na) was applied at a dose level of 5.0 mg/animal dermally to the fur-clipped dorsal area of female CD-1 mice twice weekly for 47 weeks after applications of 10 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator twice weekly for 5 weeks. A total of 25 skin tumors (21 papillomas and four carcinomas) developed in 15 out of 20 mice (75%). The incidence and yield of skin tumors in this DMBA/OPP-Na group were significantly higher than in the DMBA/acetone-treated group where only six tumors (five papillomas and one carcinoma) were observed in five out of 20 mice (25%). Only one papilloma developed in OPP-Na/12-o-tetradecanoylphorbol 13-acetate (TPA) treated animals (initiation testing group), and no tumors were observed in mice receiving OPP-Na/acetone. OPP-Na elevated 5-bromodeoxyuridine(BrdU) incorporation in basal cells of mouse epidermis dose-relatedly and the thickness of the skin in the treated group was also increased to approximately 2- or 3-fold that of controls. In addition, high dose application (20 mg/mouse) caused ulceration. O-Phenylphenol (OPP) administration was associated with extensive corrosive effects. The data suggest that OPP-Na is an ulcerogenic agent which induces epidermal proliferation and which can act as a promoter, but not as an initiator or a complete carcinogen, in two-stage mouse skin carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Synergistic effects of low-dose hepatocarcinogens in induction of glutathione S-transferase P-positive foci in the rat liver.

The effects of combined administration of hepatocarcinogens at low doses on the development of glutathione S-transferase P-form (GST-P)-positive foci of rat liver were examined utilizing a bioassay model which consists of a single injection of diethylnitrosamine (DEN, 200 mg/kg, ip), two-thirds partial hepatectomy at week 3 and a 6-week administration of test compounds. The chemicals used, 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), phenobarbital (PB), thioacetamide (TAA), N-ethyl-N-hydroxyethylnitrosamine (EHEN), benzo[a]pyrene (B[a]P), carbazole, and alpha-hexachlorocyclohexane (alpha-HCH) were incorporated in the diet, except for EHEN which was dissolved in the drinking water, at levels of 1/6 of the doses usually used. The combinations were: I) 2-AAF, 3'-Me-DAB, PB, TAA, EHEN and B[a]P, II) 2-AAF, 3'-Me-DAB and PB, III) TAA, EHEN and B[a]P, IV) 2-AAF, 3'-Me-DAB, carbazole, TAA, EHEN and alpha-HCH, V) 2-AAF, 3'-Me-DAB and carbazole, and VI) TAA, EHEN and alpha-HCH. All combinations, except for II, caused an increase in the area of the foci as evaluated by the ratios of areas in the combined administration groups to the sum totals of 3 or 6 individual data: I) 1.75, II) 0.81, III) 2.01, IV) 3.62, V) 1.34 and VI) 2.91. The non-synergistic effect in combination II might be related to PB induction of hepatic microsomal enzymes leading to enhanced enzymatical detoxification of 2-AAF and 3'-Me-DAB. The present results indicate that exposure to several chemicals of similar organotropism, even at doses lower than the apparent carcinogenic levels, might be critical to the carcinogenic process.

2-Acetylaminofluorene↗
PubMed1989

Enhancing effect of high fat diet on 4-nitroquinoline 1-oxide-induced pulmonary tumorigenesis in ICR male mice.

The effects of dietary high fat on 4-nitroquinoline 1-oxide (4NQO)-induced lung tumorigenesis were investigated in male ICR mice. Two groups of mice were initially given a single subcutaneous injection of 4NQO at a dose of 15 mg/kg and, thereafter, fed either 20% corn oil-supplemented diet or a standard basal diet. Two further groups were maintained on the high fat diet or standard diet without administration of 4NQO. Mice were killed at weeks 15, 18 and 25 and the incidence of lung tumors at each time point was found to be significantly increased in the 4NQO/high fat diet group as compared to the 4NQO/standard diet group in terms of both incidence of tumor-bearing mice and the number of lesions per mouse. The results thus indicate that dietary high fat can enhance 4NQO-induced lung tumorigenesis in mice.

4-Nitroquinoline-1-oxide↗
PubMed1989

Advantages and limitations of stereological estimation of placental glutathione S-transferase-positive rat liver cell foci by computerized three-dimensional reconstruction.

The applicability to a medium-term bioassay for liver carcinogens of mathematical formulae for the calculation of numbers of foci per volume was examined in F344 rats. Two weeks after initiation with diethylnitrosamine, animals were given test compounds for 6 weeks, partial hepatectomy being performed at week 3. At week 8, the rats were killed, the livers removed and stained immunohistochemically for assessment of glutathione S-transferase P form (GST-P)-positive foci development. Numbers and areas of lesions were measured two-dimensionally using a color image analyzer, and the Enzmann and Campbell formulae for estimation of number and volume per cm3 were applied to the results. In addition, three-dimensional reconstruction of individual foci was performed using up to 150 GST-P stained foci, with the aid of a computerized graphic system. Both two- and three-dimensionally expressed quantitative results were found to adequately demonstrate the modifying potential of test chemicals on hepatocarcinogenesis. The three-dimensional approach was only more accurate if most of the foci were small and the liver was enlarged by compound treatment. Stereological reconstruction revealed that the shape of GST-P-positive foci, especially if relatively large, is not always spherical but that many demonstrate irregular branching forms, so that the assumptions behind stereological estimation are not met. The results therefore show that care must be taken in applying mathematical formulae for the calculation of three-dimensional data.

Animals↗
PubMed1989

Comparative study of urinary bladder carcinomas in Japanese and Egyptians.

One hundred six Japanese and 169 Egyptian cases of urinary bladder carcinoma treated by total cystectomy were analyzed histopathologically. Urinary bladder carcinomas in Egypt were encountered at an earlier age than those in Japan. The proportion of carcinomas in Egyptian males was higher than in Japanese males. Squamous cell carcinomas (SCCs) predominated in Egyptian cases whereas transitional cell carcinomas predominated in Japanese cases. The pathological stage of Egyptian cancers was more advanced than in Japanese cases; even grade 1 SCCs showed invasion into the muscular layer. Most carcinomas in Egypt were associated with Schistosoma haematobium infections.

Aged↗
PubMed1989

Rapid bioassay methods for carcinogens and modifiers of hepatocarcinogenesis.

It is very important to detect environmental carcinogens in a short period. For this purpose, a rapid bioassay system based on two-step hepatocarcinogenesis has been developed in our laboratory. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.p. and, starting 2 weeks later, were treated with test compounds for 6 weeks and then sacrificed, all rats being subjected to a two thirds partial hepatectomy at week 3. Carcinogenic potential was scored by comparing the glutathione S-transferase placental form-positive foci in the liver with those of the corresponding control. More than 90% of hepatocarcinogens showed positivity, and none of the compounds reported as noncarcinogenic demonstrated positivity. Furthermore, this system also detected inhibitory effects. In order to detect nonhepatocarcinogens, other appropriate systems also have been developed, for example, using methylnitrosourea or other multispectrum carcinogens. These rapid bioassay systems are particularly useful for the screening of environmental carcinogens.

Animals↗
PubMed1989

[Twenty-eight day repeated dose toxicity testing of diphenylamine in F344 rats].

A twenty-eight day repeated dose toxicity test of diphenylamine (DPA) was carried out in male and female F344 rats at dose levels of 1000, 333, 111 or 0 mg/kg/day. Thirty-six animals of both sexes were divided into 6 groups of equal number, 4 groups being used for the 28 days dosing study and the remainder for investigation of recovery. Inhibition of body weight gain, increase of liver, spleen and kidney weights, and anemia were observed in the highest dose groups in both sexes. The same groups demonstrated mucosal hyperplasia in the forestomach, dilatation, degeneration or necrosis of renal tubules in the corticomedullary junction, and hyperplasia in the bone marrow histopathologically. Slight increase of spleen, liver and kidney weights as well as slight degeneration of renal tubules were evident in several animals receiving the dose level of 333 mg/kg/day. Repair of histopathological lesions and anemia occurred within 14-day resting period. Based on these findings, under the present experimental conditions, the no observable effect level of DPA was 111 mg/kg/day.

Administration, Oral↗
PubMed1989

[Analysis of renal calcification and stone formation in rats treated with ethoxyquin using X-ray analytical scanning electron microscopy: ultrastructural observations and element analysis].

Rat renal calcification and stone formation were investigated using a JEOL-JSM840A scanning electron microscope (SEM) equipped with a LINK-QX200J energy dispersed X-ray detector (EDX). Male Wistar rats were treated with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water or 10% NaCl in the diet for 8 weeks, and subsequently administered a dietary supplement of 0.1% ethoxyquin (EQ) for 32 weeks. An additional group received the EQ treatment alone. Calcification and stones were observed from the renal papilla to the pelvis region in all EQ treated groups. The incidence and grade of the lesion in the combined treated groups were much more greater than in the group treated with exposed to EQ alone. Ultrastructurally, microvilli on the surface of the renal papilla cells appeared degenerated or disappeared completely in the treated groups. Chemical element analysis of the renal stones revealed P and Ca to be the primary constituents. They were therefore considered to be of hydroxyapatite type.

Animals↗
PubMed1989

[Effect of vitamin A deficiency on PNUR-induced carcinogenesis in the rat upper digestive tract].

The effects of vitamin A (VA) deficiency on 1-propyl-1-nitrosourethan (PNUR)-induced tumorigenesis in the upper digestive tract were investigated in male F344 rats. Starting at 6 weeks old, animals were given PNUR in the drinking water (200 ppm) for one week, and starting 2 weeks later, were divided into 3 groups (30 rats/group) and maintained on VA-deficient diet, VA-supplemented diet (semipurified diet) or standard diet (CRF-1), respectively. An additional control group (10 rats) was fed VA-deficient diet without PNUR treatment. The experiment was terminated at 41 weeks after the beginning of PNUR administration, and development of tumors in the upper digestive tract was determined histopathologically. Squamous cell tumors were observed in the oral cavity, tongue and forestomach of all PNUR treated groups, while no tumors developed in the control group. Significantly higher incidences of forestomach papillomas were observed in the groups administered VA-deficient or VA-supplemented diets, as compared with that receiving standard diet (p less than 0.01, p less than 0.05, respectively). These results thus suggest that the higher incidences of forestomach tumors were probably due to general dietary differences (semipurified vs. standard diets) and not to the VA deficiency per se.

Animals↗
PubMed1988

Modifying effects of concomitant treatment with butylated hydroxyanisole or butylated hydroxytoluene on N,N-dibutylnitrosamine-induced liver, forestomach and urinary bladder carcinogenesis in F344 male rats.

The modifying effects of concomitant antioxidant treatment on N,N-dibutylnitrosamine (DBN)-induced carcinogenesis were investigated. Male F344 rats were given 0.05% DBN in their drinking water for 16 weeks, and simultaneously administered powder diet containing 2.0% butylated hydroxyanisole (BHA) or 0.7% butylated hydroxytoluene (BHT) for 16 weeks. Control animals received drinking water containing 0.05% DBN without antioxidant treatment. The final incidences of hepatocellular carcinomas were 100, 100 and 40% in the DBN plus BHA, DBN plus BHT and DBN treated groups, respectively, the difference being significant (P less than 0.001). Lung metastases were only observed in the DBN plus BHT group and DBN plus BHA group (50%, P less than 0.001; 7%, respectively). The incidence of papillary or nodular hyperplasia of the urinary bladder in the DBN plus BHA group was significantly higher than that of the control (P less than 0.05). Furthermore, esophageal carcinomas and papillomas were observed in all DBN treated groups, with no inter-group significant variation in yield. On the other hand, combination of DBN treatment with BHA or BHT significantly reduced the resultant incidences of forestomach hyperplasia. The results clearly demonstrated that concomitant administration of antioxidants, and in particular BHT, can modify DBN carcinogenesis.

Animals↗
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

Combined effects of L-ascorbic acid, citric acid or their sodium salts on tumor induction by N-butyl-N-(4-hydroxybutyl)nitrosamine or N-ethyl-N-(4-hydroxybutyl)nitrosamine in the rat urinary bladder.

L-Ascorbic acid, citric acid or their sodium salts (at levels equivalent to 5% sodium L-ascorbate) were fed in the diet simultaneously with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) (0.025% BBN or 0.021% EHBN) in the drinking water to male F344 rats for 20 weeks to determine whether urinary pH changes affect the carcinogenicity of BBN or EHBN. In the urine, pH was decreased in rats fed the acidic chemicals and increased in rats fed their corresponding sodium salts. Histopathologically, the incidences and numbers of preneoplastic and neoplastic lesions in groups treated with each test chemical were not different from those in control groups except for sodium citrate-treated groups in which induction of carcinomas was higher, resulting from increased intake of either carcinogen and also from increased urinary excretion of main carcinogenic metabolites. These results show that the test chemicals do not affect the carcinogenicity of BBN or EHBN on the rat urinary bladder when simultaneously administered despite significant differences in urinary pH.

Animals↗