Biomedical subjects

M Asamoto

Publications and source records attributed to M Asamoto.

At least 91 records · Page 5Linked to original sources

PubMed1989

Immunohistochemical expression of keratin proteins in urinary bladder carcinoma.

Transitional carcinomas of the urinary bladder were examined immunohistochemically for keratin proteins with the use of polyclonal antiserum (TK, 41-65 kDa) and 3 monoclonal antibodies (KL 1, 55-57 kDa; PKK 1, nos. 19, 18, 8; and K 8.12, nos. 16, 13). Umbrella cells gave particularly strong staining for TK, KL 1 and PKK 1, whereas they were negative for K 8.12. Basal- and intermediate-layer cells in urothelial epithelium were moderately positive for all keratins. Brunn's nests cells showed comparatively slight or moderate keratin staining, and K 8.12 staining of Brunn's nests was higher than in urothelial epithelial cells. Transitional carcinoma (grades I and II) indicated uniform keratin distribution, and staining was strong with TK, while that of KL 1, PKK 1 and K 8.12 varied, and grade III tumors showed the lowest intensity of staining. K 8.12 staining in papillary transitional carcinomas was strongly positive in basal located tumor cells, as compared with apical tumor cells. Squamous cell carcinoma was varying positive to keratin reactions dependent on the degree of keratinization. Heterogenity of keratin distribution in papillary transitional carcinomas was given between basal tumor cells and well differentiated tumor cells including umbrella-like cells.

Antibodies, Monoclonal↗

PubMed1989

Strain differences in susceptibility to 2-acetylaminofluorene and phenobarbital promotion of rat hepatocarcinogenesis in a medium-term assay system: quantitation of glutathione S-transferase P-positive foci development.

Strain differences in susceptibility to promotion by the liver carcinogens 2-acetylaminofluorene (2-AAF) and phenobarbital (PB) were examined in the medium-term bioassay system initially developed in our laboratory using male F344 rats as the test animal and glutathione S-transferase placental form (GST-P)-positive foci as the lesion end-point. Numbers and areas per cm2 of induced GST-P-positive hepatocellular foci were compared in LEW, F344, NAR, SD, WBN, SHR, Wistar and ODS rats initiated with diethylnitrosamine (DEN) and subjected to partial hepatectomy during subsequent administration of 2-AAF or PB. LEW, SD, WBN, and F344 rats were most susceptible to hepatopromotion by both compounds, with a hundred fold increase in lesion area being observed for 2-AAF in the LEW case. NAR and SHR strains demonstrated an intermediate response, while Wistar and, in particular, the related ODS rats demonstrated very low susceptibilities. The obvious strain differences could be expressed in terms of comparative indices of promoting effects of 2-AAF and PB as well as DEN itself regarding each of the 8 strains tested. The use of F344 rats for the bioassay model was validated by the relatively high sensitivity to both DEN and 2-AAF initiation as well as second-stage promotion stimulus exhibited.

2-Acetylaminofluorene↗

PubMed1989

Strain differences in susceptibility to 2-acetylaminofluorene and phenobarbital promotion of hepatocarcinogenesis: immunohistochemical analysis of cytochrome P-450 isozyme induction by 2-acetylaminofluorene and phenobarbital.

Strain differences in the expression of cytochrome P-450 isoenzymes (P-450s) during enhancement of hepatocarcinogenesis by 2-acetylaminofluorene (2-AAF) and phenobarbital (PB) were investigated immunohistochemically using monoclonal antibodies against phenobarbital (PB) (APF3) or 3-methylcholanthrene (3-MC) (APH8) inducible P-450s. LEW, SD, WBN, F344, SHR, NAR, Wistar and ODS rats were studied, the first five strains proving to be less susceptible to 2-AAF induction of APH8 while responding strongly to the promoting influence of this chemical, as reported previously. The other three strains, NAR, Wistar and ODS, demonstrated greater inducibility, this correlating with an observed resistance to promotion by 2-AAF. PB administration was not associated with any strain difference in APF3 cytochrome P-450 inducibility except in the ODS rat, in which its effects were minimal. The results provide direct evidence that differential expression of cytochrome P-450 species plays a major role in determining responsiveness to hepatocarcinogenesis-promoting agents such as 2-AAF.

2-Acetylaminofluorene↗

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↗

PubMed1988

Effect of modifying agents on the phenotypic expression of cytochrome P-450, glutathione S-transferase molecular forms, microsomal epoxide hydrolase, glucose-6-phosphate dehydrogenase and gamma-glutamyltranspeptidase in rat liver preneoplastic lesions.

The expression of A and P forms of glutathione S-transferase (GST-A and P), two cytochrome P-450 isoenzymes (P-450 PB3a and P-450 MC2), microsomal epoxide hydrolase (mEHb), glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyltranspeptidase (gamma-GT) was compared in preneoplastic liver lesions and background parenchyma of F344 rats post-treated with butylated hydroxyanisole (BHA), ethoxyquin (EQ) or acetaminophen (AAP). These latter three compounds have been shown to inhibit hepatocarcinogenesis after initial treatment with N-ethyl-N-hydroxyethylnitrosamine (EHEN) and a significant decrease in the number of enzyme-altered foci and nodules positive for GST-P, GST-A, G6PD and gamma-GT and negative for P-450 PB3a, P-450 MC2 was associated with their administration. Whereas in the foci case the decrease was most prominent for non-discrete (heterogeneous) type lesions, the results of quantitation of nodules revealed a most significant alteration in the discrete homogeneously staining population. This indicates that BHA, EQ and AAP have the potential to inhibit the growth of the phenotypically stable lesions thought most likely to be the immediate precursors of hepatocellular carcinomas. The two anti-oxidants were associated with periportal increase of all enzymes investigated, whereas AAP induced GST species and mEHb in the perivenular zone. Irrespective of slightly elevated enzyme levels in surrounding parenchyma, mEHb antibody binding levels within lesions showed a reciprocal shift from positive to negative in rats treated with BHA, EQ and AAP.

Animals↗

PubMed1988

Positive influence of dietary deoxycholic acid on development of pre-neoplastic lesions initiated by N-methyl-N-nitrosourea in rat liver.

The effect of deoxycholic acid (DCA) treatment subsequent to initiation of F344 male rats with N-methyl-N-nitrosourea (MNU), a wide spectrum carcinogen inducing tumors in many organs, was investigated. Rats were initially given four doses of MNU (50 mg/kg) i.p. within a 2-week period combined with a two-thirds partial hepatectomy performed at day 7 and then placed on basal diet containing DCA at concentrations of 0.313, 0.125, 0.050 and 0.020% for 21 weeks prior to final sacrifice. All organs studied were carefully examined histologically and histochemically for development of neoplastic and pre-neoplastic lesions. DCA enhanced the induction of glutathione S-transferase positive (GST-P+) liver cell foci in a dose-related manner. Furthermore groups of rats given DCA without prior MNU administration also developed dose-dependent numbers of pre-neoplastic liver lesions. In addition, increased numbers of small intestine tumors were apparent in DCA-treated animals although the difference was not significant. Induction of tumors in the thyroids, Zymbal glands, skin and peripheral nerves was not affected. The results indicate that DCA is a strong promoter of hepatocarcinogenesis with possible complete carcinogenicity in the liver and promotion potential for tumor development in the small intestine.

Animals↗

PubMed1988

Primary choriocarcinoma of the urinary bladder.

A case of choriocarcinoma of the urinary bladder is presented. A 57-year-old man underwent a cystectomy for transitional cell carcinoma, grade II. Choriocarcinoma was found, in addition to the transitional cell carcinoma, in the removed urinary bladder. After the operation, metastases appeared in both lungs, evolving rapidly despite chemotherapy. The patient died five months after admission. Immunohistochemically, staining for human placental lactogen was strongly positive, and both alpha and beta subunits of human chorionic gonadotropin were weakly positive in the primary site of the removed urinary bladder and in the metastatic foci.

Carcinoma, Transitional Cell↗

PubMed1988

A new medium-term bioassay system for detection of environmental carcinogens using diethylnitrosamine-initiated rat liver followed by D-galactosamine treatment and partial hepatectomy.

The effects of D-galactosamine on induction of preneoplastic glutathione S-transferase placental form positive liver foci were investigated in F344 rats pretreated with diethylnitrosamine (DEN) in an attempt to improve the predictive value of the medium-term bioassay system developed in our laboratory. Two weeks after the initial single ip dose (200 mg/kg) of DEN, administration of test compounds was commenced simultaneously with an ip injection of D-galactosamine at a dose of 300 mg/kg body wt. All rats were then subjected to two-thirds partial hepatectomy (PH) at week 5 and sacrificed for assessment of lesion yield at week 8. Measurement and comparison of the numbers and areas of glutathione S-transferase placental form positive (GST-P+) foci per cm2 revealed a positive response to more carcinogens, including non-hepatocarcinogens, than did the same bioassay system without injection of D-galactosamine. Thus the results suggest that inclusion of this extra proliferative stimulus may improve the medium-term detection of carcinogens and modifiers.

Animals↗

PubMed1988

Dose-dependent induction of liver and thyroid neoplastic lesions by short-term administration of 2-amino-3-methylimidazo[4,5-f]quinoline combined with partial hepatectomy followed by phenobarbital or low dose 3'-methyl-4-dimethylaminoazobenzene promotion.

Dietary administration of 0.1, 0.05, or 0.025% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for two weeks combined with partial hepatectomy at the end of the first week and followed by long-term treatment with phenobarbital (PB) or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) from week 3 to week 86 resulted in dose-dependent development of liver and thyroid neoplastic and preneoplastic lesions. Quantitation of glutathione S-transferase placental form (GST-P)-positive hepatocellular focal populations revealed a significant correlation of IQ concentration with lesion area, with a yield approximately equal to that generated by a similar dose of 2-acetylaminofluorene. The fact that IQ was less toxic therefore allowed greater yields of hepatocellular carcinomas to be induced. The development of thyroid tumors initiated by the IQ treatment was significantly enhanced by the administration of PB, whereas Zymbal gland tumors induced by IQ did not show any correlation with either PB or 3'-Me-DAB treatment.

2-Acetylaminofluorene↗

PubMed1987

Regression of simple hyperplasia and papillomas and persistence of basal cell hyperplasia in the forestomach of F344 rats treated with butylated hydroxyanisole.

The reversibility of forestomach lesions induced in rats by butylated hydroxyanisole (BHA) was examined. F344 rats were given a 2% BHA diet for 24, 48, or 72 wk followed by a basal diet for the remainder of the 96-wk experiment. Two other groups of rats were given a 2% BHA diet or basal diet alone for 96 wk. The forestomach lesions at wk 24, 48, 72, or 96 were compared histopathologically. The results showed that exophytic epithelial proliferation (simple hyperplasia or papilloma) induced by BHA was reversible, while endophytic proliferation of basal cells (basal cell hyperplasia) persisted after withdrawal of BHA administration. This suggests that simple hyperplasia and papilloma of the forestomach induced by BHA are not autonomous and need continuous feeding of BHA to develop further.

Animals↗

PubMed1987

Metabolism of 2- and 3-tert-butyl-4-hydroxyanisole (2- and 3-BHA) in the rat. (II): Metabolism in forestomach and covalent binding to tissue macromolecules.

The mechanism of action of 2(3)-tert-butyl-4-hydroxyanisole (2-BHA or 3-BHA) on rat forestomach epithelium was studied by examining the metabolites of BHA in the stomach and the covalent binding of BHA to macromolecules in the forestomach epithelium. Male F344 rats 6 weeks old were given a single intragastric injection of 1 g/kg body wt of [tert-14C]-3-BHA (Bu-3-BHA) or [methyl-14C]-3-BHA (Me-3-BHA), and 6 h later BHA metabolites in the forestomach, glandular stomach and stomach contents were examined by thin-layer chromatography. No significant amounts of metabolites were detected in the forestomach or glandular stomach epithelium and almost all the radioactivity in these tissues was extracted with organic solvents. In in vitro experiments also, no significant amounts of metabolites were detected when the 9000 g supernatant of the forestomach or glandular stomach epithelium, or gastric juice was incubated with Bu-3-BHA in the absence or presence of NADPH. In binding studies, rats were given Bu-3-BHA, [tert-14C]-2-BHA (Bu-2-BHA), Me-3-BHA or [methyl-14C] butylated hydroxytoluene (Me-BHT) intragastrically at a dose of 1 g/kg body wt with or without pretreatment with unlabelled 1% 3-BHA or BHT in the diet for 6 days. Six hours after treatment with a labelled compound, the rats were sacrificed and the DNA, RNA and protein of their forestomach, glandular stomach, liver and kidney were isolated. Bu-3-BHA, Bu-2-BHA and Me-3-BHA did not bind covalently to forestomach DNA or RNA, and the amounts of radioactivity of these compounds bound to proteins in the 4 tissues were similar. These findings suggest that BHA acts on the forestomach epithelium directly without metabolic activation, and that its action is not related to its binding to DNA or RNA.

Animals↗

PubMed1987

Lack of tumorigenic response in the prostate gland of castrated F344 rats by 3,2'-dimethyl-4-aminobiphenyl given with methyltestosterone.

In an attempt to induce a high incidence of prostate carcinoma, 3,2'-dimethyl-4-aminobiphenyl (DMAB), a prostatic carcinogen, was given during the period of cell proliferation of the prostate gland induced by the administration of methyltestosterone (MT) to castrated F344 rats. Three weeks after the surgical castration, rats were given diet containing 300 ppm of MT for 2 weeks and basal for 2 weeks alternately 12 times. During each treatment with MT, one (group 1) or two (group 2) subcutaneous injections of 50 mg/kg body wt. of DMAB was given. After the last treatment of MT, a pellet of testosterone propionate (TP) was implanted in the subcutis of all animals until the end of the experiment (week 60). No carcinomas developed in the prostate gland of any of the rats. Atypical hyperplasia of the ventral lobe of prostate was found in 4 of 22 rats in group 1 and 2 of 20 rats in group 2. The incidences of atypical hyperplasia of the seminal vesicles in groups 1 and 2 were 64% and 75%, respectively. No pathological lesions in the prostate were observed in 32 rats given DMAB without MT treatment.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1987

Immunohistochemically demonstrated altered expression of cytochrome P-450 molecular forms and epoxide hydrolase in N-ethyl-N-hydroxyethylnitrosamine-induced rat kidney and liver lesions.

A comparison of N-ethyl-N-hydroxyethylnistrosamine (EHEN)-induced preneoplastic and neoplastic lesions in the rat liver and kidney was made with respect to the expression of different drug metabolizing enzymes. Four cytochrome P-450 species (cyt. P-450 UT50, PB3a, MC1 and MC2) and microsomal epoxide hydrolase (mEHb) were investigated along with two glutathione S-transferase species (GST-P and A forms) earlier shown to be elevated in putative preneoplastic lesions in the liver and kidney, respectively. In contrast to the liver lesions, which showed clear decrease in all forms of cyt. P-450s and increase of mEHb, elevated levels of cyt. P-450 PB3a and, to a lesser extent, the other P-450 forms and early elevation to late decrease in mEHb characterized the renal tubular lesions. Thus opposite shift in enzyme phenotype was observed in carcinogen-induced focal lesions of the two organs. Variation in binding levels in the different nephron segments and zones of the liver acinus indicated physiological specialization with regard to the enzymes investigated and suggested that the altered phenotype of preneoplastic populations might be of adaptive significance.

Animals↗

PubMed1987

Enhancing effects of N-ethyl-N'-nitro-N-nitrosoguanidine and sodium taurocholate on development of pepsinogen 1 decreased pyloric glands in rats initiated with N-methyl-N'-nitro-N-nitrosoguanidine.

Sequential quantitative analyses were made of pepsinogen 1 (Pg 1) decreased pyloric glands after treating male WKY rats first with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and then with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) as a second gastric carcinogen or sodium taurocholate (Na-TC) as a gastric promoter. Animals received a single dose of MNNG (160 mg/kg body weight) by gastric intubation followed two weeks later by either ENNG in drinking water (100 micrograms/ml) (group 1), basal diet containing 0.25% Na-TC (group 2), or basal diet and tap water (group 3), from weeks 3 to 24. Animals were sacrificed at weeks 8, 12, 16, 20 and 24. Sections of the pyloric mucosa were investigated for Pg 1 immunostaining. In comparison with group 3, induction of Pg 1 decreased pyloric glands was significantly enhanced by ENNG from week 8 and by Na-TC from week 16. The former exerted a significantly stronger effect at each time point. The results suggest that Pg 1 decreased pyloric glands represent a good marker for early detection of gastric carcinogens and promoters in in vivo test systems.

Animals↗

PubMed1986

Promoting effects of various agents in rat urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effects of various chemicals on the development of neoplastic lesions in the urinary bladder were investigated in male F344 rats given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as an initiator in their drinking water for 4 weeks. The compounds tested, indomethacin, acemetacin, epsilon-aminocaproic acid (EACA), diphenyl, allopurinol and acetaminophen (AAP), were added to the diet or drinking water for 32 weeks, and all animals were killed at the end of week 36. Of the chemicals tested, only diphenyl significantly increased the incidences and average numbers (per 10 cm basement membrane) of papillary or nodular hyperplasias (PN hyperplasia), papillomas and carcinomas of the urinary bladder over those in animals treated with BBN alone. These findings show that diphenyl is a promoter of urinary bladder carcinogenesis in male F344 rats.

Acetaminophen↗

PubMed1986

Comparison of the effects of 13 phenolic compounds in induction of proliferative lesions of the forestomach and increase in the labelling indices of the glandular stomach and urinary bladder epithelium of Syrian golden hamsters.

Groups of 6-week-old male Syrian golden hamsters were given 13 different phenolic compounds for 20 weeks. Of these compounds, 2(3)-tert-butyl-4-methoxyphenol (BHA), 2-tert-butyl-4-methylphenol (TBMP) and p-tert-butylphenol (PTBP) strongly induced hyperplasia and tumorous lesions in the forestomach. Catechol, p-methylphenol (PMYP), p-methoxyphenol (PMOP), caffeic acid, methylhydroquinone (MHQ) and pyrogallol were less active, and resorcinol, hydroquinone, propylparabene and tert-butylhydroquinone (TBHQ) were not active. The labelling index in the forestomach epithelium was significantly increased by addition to the diet of BHA, TBMP, catechol, PMOP, PTBP and MHQ. PMOP induced epithelial damage and regenerative hyperplasia of the pyloric region. Catechol, caffeic acid and PMYP induced similar though less marked lesions. The labelling index in the glandular stomach was significantly increased by oral catechol (P less than 0.05) or PMOP (P less than 0.05). No histopathological lesions were observed in the urinary bladder epithelium, but propylparabene (P less than 0.05), catechol, TBHQ and MHQ increased the labeling index. These findings indicate that PTBP and TBMP may be carcinogenic for hamster forestomach after long-term administration, and that both one hydroxy and tert-butyl substituents may be important for induction of hamster forestomach tumors.

Animals↗

PubMed1986

Modifying effects of antioxidants on chemical carcinogenesis.

Studies were made on the carcinogenic activity of butylated hydroxyanisole (BHA) in rats, mice, and hamsters and the effect of the antioxidants BHA, butylated hydroxytoluene (BHT), ethoxyquin (EQ), sodium L-ascorbate (SA), ascorbic acid (AA), sodium erythorbate (SE), propyl gallate (PG), and alpha-tocopherol, on two-stage chemical carcinogenesis in rats initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 1,2-dimethylhydrazine (DMH), diethylnitrosamine (DEN), 7,12-dimethylbenz(a)anthracene (DMBA), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), N-ethyl-N-hydroxyethylnitrosamine (EHEN), or N-methylnitrosourea (MNU). BHA clearly induced squamous cell carcinomas in both the rat and hamster forestomach. The tumorigenic action of crude BHA on the forestomach is largely due to 3-tert-BHA. In two-stage chemical carcinogenesis, BHA promoted MNNG or MNU-initiated forestomach and BBN- or MNU-initiated urinary bladder carcinogenesis and inhibited DEN- or EHEN-initiated liver and DMBA-initiated mammary carcinogenesis. BHT demonstrated promotion potential for urinary bladder and MNU-initiated thyroid carcinogenesis and inhibited DMBA-initiated ear duct carcinogenesis. EQ promoted EHEN-initiated kidney carcinogenesis and inhibited DMBA-initiated mammary and EHEN-initiated liver carcinogenesis. SA promoted forestomach and urinary bladder carcinogenesis and SE likewise enhanced urinary bladder carcinogenesis. alpha-Tocopherol inhibited ear duct carcinogenesis. No effects of any of the antioxidants on glandular stomach carcinogenesis were found. The results clearly demonstrated that antioxidants have different effects (promoting or inhibitory influences) depending on the organ studied and suggest the importance of a whole body approach to their investigation.

Animals↗

PubMed1986

Disappearance of upward proliferation and persistence of downward basal cell proliferation in rat forestomach papillomas induced by butylated hydroxyanisole.

The reversibility of forestomach lesions induced in rats by butylated hydroxyanisole (BHA) was examined. F344 rats were given BHA for 24 weeks, followed by the basal diet, and their forestomach lesions at weeks 24 and 96 were compared histopathologically. Hyperplasias and papillomas showing upward proliferation were found in week 24 but not in week 96. However, downward proliferation of basal cells persisted after the discontinuation of BHA administration. This finding suggests that downward growth of basal cells is not reversible and is important in the development of BHA-induced forestomach tumors in rats.

Animals↗