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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 559 records · Page 31Linked to original sources
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

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

Dose-dependent effects of butylated hydroxyanisole, butylated hydroxytoluene and ethoxyquin for promotion of bladder carcinogenesis in N-butyl-N-(4-hydroxybutyl)nitrosamine-initiated, unilaterally ureter-ligated rats.

Dose-dependent effects of 3 antioxidants, butylated hydroxyanisole (BHA, 2.0, 1.0 and 0.5%), butylated hydroxytoluene (BHT, 1, 0.5 and 0.25%) and ethoxyquin (0.5, 0.25 and 0.125%) on the development of preneoplastic lesions in the bladder of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-treated rats were investigated. Feeding of the antioxidants after pretreatment of 0.05% BBN commenced and unilateral ureteric ligation was combined at week 3 of the experiment. Surviving rats were killed at the end of week 24. BHA and BHT, but not ethoxyquin increased dose-dependently the incidence and number of preneoplastic lesions, papillary or nodular hyperplasia of the urinary bladder in rats treated with BBN. Particularly, the incidence and number of PN hyperplasia in rats treated with 2.0% BHA and 1.0% BHT were significantly higher than those of the control group. Thus, promoting activities of BHA and BHT, but not ethoxyquin for the urinary bladder were confirmed in this system of BBN-initiated, unilaterally ureter-ligated rats.

Animals↗
PubMed1987

Synergistic inhibitory effects of dipyridamole and vincristine on the growth of human leukaemia and lymphoma cell lines.

The effects of combinations of dipyridamole, an effective blocker of the salvage pathway of DNA synthesis, and 8 types of anti-cancer drugs on the growth of human T, B and myeloid leukaemia/lymphoma cell lines in vitro were examined. In combinations, dipyridamole and vincristine (VCR), and dipyridamole and vindesine had synergistic inhibitory effects. Dipyridamole reduced the efflux of VCR from cells and enhanced their VCR accumulation in a dose-dependent manner at concentrations of up to 10 microM in the lymphoid cell lines, MOLT-3 and BL-TH, and of up to at least 20 microM in the myeloid cell line, ML-1. Dipyridamole also enhanced the accumulation of VCR in PHA-stimulated and un-stimulated lymphocytes of normal donors, but efflux of VCR was more rapid from normal lymphocytes than from cultured cell lines. It is proposed that combination therapy with dipyridamole plus VCR should be effective in the treatment of leukaemia and lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Organ specific modifying potential of ethinyl estradiol on carcinogenesis initiated with different carcinogens.

Estrogen has been shown to exert a modifying potential on carcinogenesis in various organs, and in particular the hormone-dependent tissues. The present experiments were carried out to determine the effects of post-initiation phase administration of ethinyl estradiol (EE) on tumor development in the liver, kidney, lung, thyroid, bladder and esophagus of male F344 rats. Animals were initiated by 2 weeks treatment with 0.05% N-bis(2-hydroxypropyl)nitrosamine (DHPN), 0.1% N-ethyl-N-hydroxyethylnitrosamine (EHEN), 0.03% N-nitrosopiperidine (NPD), 0.02% 2-acetylaminofluorene (2-AAF) or 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their diet or drinking water, and starting 1 week after initiation, they were given diet with or without a 0.001% EE supplement for 49 weeks, at which point the experiment was terminated. EE significantly increased the development of tumors of the liver (DHPN-, EHEN-, 2-AAF- and NPD-treated groups) and kidneys (EHEN-treated group) but inhibited their development in the lungs (DHPN-treated group) and urinary bladder (BBN-treated group). In the liver, EE also increased the development of glutathione S-transferase P type-positive lesions to various extents depending on the initiator used. EE administration was associated with a decreased incidence of esophageal hyperplasia in the EHEN-initiated group but an opposite increase in the NPD-initiated animals. No effect of EE was evident regarding thyroid lesions.

2-Acetylaminofluorene↗
PubMed1987

Effects of simultaneous treatment with various chemicals on BHA-induced development of rat forestomach hyperplasia--complete inhibition by diethylmaleate in a 5-week feeding study.

Male F344 rats were administered phenobarbital, polychlorinated biphenyl (PCB), retinol acetate, indomethacin, 6-amino-caproic acid, dexamethasone (DEX) or diethylmaleate (DEM) for one week and then were treated with these chemicals plus butylated hydroxyanisole (BHA) for a further four weeks. Histopathologically, the incidence of BHA-induced forestomach hyperplasia was significantly lower in rats treated with PCB, DEX or DEM than in those treated with BHA alone. However, the inhibition by PCB and DEX was only partial and might have been due to decreased food intake. On the other hand, DEM completely inhibited the hyperplastic response to BHA at a dose of 0.25%, and even at lower doses it demonstrated significant inhibition without any decrease in body weight or food intake. The result that DEM, a tissue glutathione depleting agent, can inhibit BHA-associated forestomach hyperplasia strongly suggests that tissue glutathione may be intimately involved in the induction of forestomach hyperplasia by the antioxidant in rats.

Aminocaproic Acid↗
PubMed1987

Enhancement of BHA-induced proliferative rat forestomach lesion development by simultaneous treatment with other antioxidants.

Synergistic effects of butylated hydroxyanisole (BHA) and other antioxidants on induction of rat forestomach lesions were investigated. Groups of F344 male rats were treated with 1% BHA plus 0.7% butylated hydroxytoluene (BHT), 1% BHA plus 1% propyl gallate (PG), 1% BHA plus 1% sodium L-ascorbate (SA), 1% BHA plus 1% DL-alpha-tocopherol (alpha-TP), 0.4% BHT plus 0.4% BHA plus 0.4% PG plus 0.4% SA plus 0.4% alpha-TP, 1% BHA or 2% BHA. Further groups of 10 rats each received antioxidants without BHA as controls. Histological examination revealed significantly increased incidences of hyperplasia in the groups given BHA together with SA or PG at the prefundic region or at the mid region respectively. The forestomach changes induced by BHA together with SA were equal to those induced by 2% BHA. On the other hand, simultaneous treatment with BHA and PG or alpha-TP reduced the incidence of hyperplasia at the prefundic region. It is concluded that mixed treatment with BHA and other antioxidants exerted enhancing or inhibitory effects on the induction of hyperplasia at different sites of the forestomach epithelium.

Animals↗
PubMed1987

Histochemical demonstration of colonic type mucin in glandular metaplasia and adenocarcinoma of the human urinary bladder.

Mucin in normal, metaplastic and neoplastic tissue specimens of the human urinary bladder was examined histochemically by the periodic acid-borohydride/potassium hydroxide/periodic acid-Schiff (PB/KOH/PAS) reaction and paradoxical concanavalin A (Con A) staining, both of which have been reported to detect mucins that are specific for the lower gastrointestinal tract. Normal mucosa, Brunn's nest, squamous metaplasia, transitional cell carcinoma, and squamous cell carcinoma produced only small amount of mucin and were negative for both PB/KOH/PAS and labile class III by Con A staining. However, several sections of mucin-producing metaplastic bladder lesions and many samples of adenocarcinoma arising from vesical mucosa and urachus contained PB/KOH/PAS-positive and/or labile class III mucin. Thus the colonic type mucin appeared in some materials of both benign and malignant mucin-producing lesions of the urinary bladder. The findings would be related to the embryogenesis of this organ.

Adenocarcinoma↗
PubMed1987

Immunohistochemical study of pancreatoblastoma.

Three cases of pancreatoblastoma in children were examined immunohistochemically and the results were compared with those of pancreatic duct carcinoma in adults. The pancreatoblastoma demonstrated positive reactions to alpha-fetoprotein (AFP) (67%: 2/3), alpha-1-antitrypsin (AAT) (100%: 3/3), carcinoembryonic antigen (CEA) (67%: 2/3) and keratin (33%: 1/3), although CEA was only weakly positive in both cases. On the other hand, adult pancreatic duct carcinoma showed positive reactions as follows; AFP: 3% (1/29), AAT: 21% (6/29), CEA: 97% (28/29) and keratin: 93% (27/29). Also, endocrine substances including insulin, glucagon and somatostatin were all negative in the pancreatoblastomas. Two cases of pancreatoblastoma which were immunohistochemically positive for AFP also showed elevation of the serum AFP level clinically. The different expressive pattern of oncofetal antigens in pancreatoblastoma as compared with pancreatic duct carcinoma in adults may provide further supporting evidence for the embryonic nature of pancreatoblastoma, and suggests that such a pattern might be used as a tumor marker for pancreatoblastoma.

Adult↗
PubMed1987

Induction of forestomach lesions in rats by oral administrations of naturally occurring antioxidants for 4 weeks.

The effects of naturally occurring antioxidants on rat forestomach epithelium were compared with those of synthetic antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), of which the former is a known forestomach carcinogen. Groups of five F344 male rats were given diet containing BHA, BHT, gallic acid, syringic acid, sesamol, caffeic acid, chlorogenic acid, ferulic acid, eugenol or esculin for 4 weeks at a level of 0.7% for BHT or 2% for other compounds. Histological examination of the forestomach showed that BHA induced hyperplasia mainly in the prefundic region near the esophageal orifice, caffeic acid induced pronounced hyperplasia throughout the forestomach epithelium, and sesamol induced large ulcers and hyperplasia in the central region. Thus, these naturally occurring antioxidants showed different toxicities and abilities to induce hyperplasia in the rat forestomach.

Animals↗
PubMed1987

Epithelial lesions of the urinary bladder in three hundred and thirteen autopsy cases.

Urinary bladders that appeared normal macroscopically were obtained from 313 autopsy cases of both sexes and examined microscopically. Proliferative lesions such as Brunn's nests and cystitis glandularis were frequent in cases of all ages and both sexes. Metaplastic lesions such as columnar or cuboidal metaplasia and squamous metaplasia were less frequent. These two types of lesions were not related to age, but squamous metaplasia was more common in females than in males. The sites of predilection for these 4 types of lesions were the trigone and anterior wall. Hyperplasia was observed in 16.3% of the male and 10.6% of the female cases, and dysplasia in 6.8% of the male and 5.7% of the female cases. Both types of lesions were more frequent in older than younger cases. Neither type of lesions was related to chronic inflammation. One case of carcinoma in situ was found in a male. These data and mapping of the bladders indicated that none of these benign proliferative and metaplastic lesions were related with the development of dysplasia or carcinoma in situ.

Adult↗
PubMed1987

Catechol strongly enhances rat stomach carcinogenesis: a possible new environmental stomach carcinogen.

Catechol (CAS: 120-80-9) is present in the environment, being a major industrial chemical as well as a major phenolic component of cigarette smoke. Continuous oral treatment of rats with 0.8% catechol for 51 weeks after a single intragastric dose of 150 mg/kg of N-methyl-N'-nitro-N-nitrosoguanidine strongly enhanced both forestomach and glandular stomach carcinogenesis. In addition, and more importantly, catechol alone induced adenocarcinoma and adenomatous hyperplasia in the pyloric region of the glandular stomach. These results clearly indicate that this environmental contaminant merits classification as an enhancer of forestomach and glandular stomach carcinogenesis with complete carcinogenic potential for the glandular stomach. Its significance for gastric tumor development in man requires elucidation.

Adenocarcinoma↗