Search PubMed⌕ Search

Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 631 records · Page 35Linked to original sources

Promotive effects of steroids and bile acids on hepatocarcinogenesis initiated by diethylnitrosamine.

The ability of four steroids and three bile acids to promote the appearance of hyperplastic foci and hyperplastic nodules initiated by diethylnitrosamine (DEN) in the liver of male Fischer rats was tested and compared with that of the known promoter phenobarbital (PB, 0.05%) as a standard value. Two weeks after a single dose of 200 mg of DEN per kg, the animals were exposed to test chemicals for 10 weeks. At 4 weeks following DEN, all treatment groups were subjected to partial hepatectomy. Of the steroids tested at the maximum tolerable doses, as determined in preliminary experiments, ethinyl estradiol was the most potent promoter, inducing more hyperplastic nodules than did PB and almost 50% less gamma-glutamyl transpeptidase-positive foci. However, gamma-glutamyl transpeptidase-positive foci induced by ethinyl estradiol were twice the average size as those induced by PB. The steroids testosterone, cortisone, and dexamethasone induced more foci than did DEN alone, but few if any hyperplastic nodules. Deoxycholic acid was the most potent promoter of the bile acids tested, including 3 to 4 times more hyperplastic nodules than did PB and more gamma-glutamyl transpeptidase-positive foci, which were 5 times larger on the average than those induced by PB. The other bile acids tested, lithocholic acid and taurine, induced slightly more foci than did DEN alone but no hyperplastic nodules. These findings suggest that ethinyl estradiol and deoxycholic acid are relatively strong promoters of the appearance of preneoplastic lesions in hepatocarcinogenesis.

Animals↗

Sequential changes in tumor development induced by 1,4-dinitrosopiperazine in the nasal cavity of F344 rats.

Tumor development was examined sequentially in the nasal cavity of male F344 rats given 0.01% 1,4-dinitrosopiperazine (DNP) in their drinking water for various periods. Rats were sacrificed at 10-week intervals for up to Week 50. On continuous DNP administration, simple hyperplasia of the nasal cavity epithelium was observed from Week 10, papillary hyperplasia, nodular hyperplasia, and papilloma was observed from Week 20, and carcinoma was observed from Week 30. Carcinoma was observed in 100% of the animals given DNP for 50 weeks. The carcinomas were adenocarcinomas (86%), adenosquamous cell carcinomas (10%), and undifferentiated carcinomas (4%). Simple hyperplasia was distributed evenly in the nasal cavity. Seventy % of the nodular hyperplasias and 81% of the carcinomas were located in the ethmoturbinate and about 75% of the papillary hyperplasias and papillomas were located in the nasoturbinate and maxilloturbinate. These findings suggest that nodular hyperplasia is very important as a precursor of carcinoma in the nasal cavity of rats treated with DNP and that papilloma is less important in relation to carcinoma development.

Animals↗

Induction of preneoplastic and neoplastic lesions in rats treated N-nitroso compounds.

Dose-related changes of incidences of pre-neoplastic and neoplastic lesions in the liver or urinary bladder were examined with N-nitroso-dimethylamine (NDMA) or N-nitrosobutyl-4-hydroxybutylamine (NBHA) respectively. The incidences of lesions by the two carcinogens were compared in short-term and long-term experiments. In a short-term experiment, rats were given a basal diet containing NDMA at concentrations of 10.0, 1.0 and 0.1 mg/kg for 6 weeks, after initiation by a single i.p. injection of N-nitrosodiethylamine (NDEA). Similar, long-term experiments (96 weeks) were also performed, but without NDEA pretreatment. A clear dose-related effect was found in the induction of pre-neoplastic lesions when the groups given 10.0 and 1.0 mg/kg NDMA were compared. This coincided with the results of a long-term experiment on the induction of hyperplastic nodules and hepatocellular carcinomas. Various concentrations of 0.05 to 0.005% of NBHA in the drinking water were given for different periods up to 12 weeks, in a short-term, and up to 40 weeks in a long-term experiment. Incidences of early preneoplastic lesions of the cell surface observed by scanning electron microscopy showed a tendency to increase with longer duration and higher dose (0.01 to 0.05%). A clear dose-dependent effect was found for the incidence of papilloma and carcinoma in the groups subjected to longer treatments.

Animals↗

Objective pathological diagnosis of coal worker's pneumoconiosis.

Pertinent pathological features of lungs obtained at autopsies from 99 coal miners were compared with those observed in the lungs of 268 male town dwellers of comparable age who were not occupationally related to the coal mining or other industries at risk for development of pneumoconiosis. The degree of anthracotic pigment deposition and severity of type of pigmented lesion with its accompanying reticulum fiber formation and fibrosis were significantly greater in lungs of miners. There was a high degree of overlap in degree of pigment deposition, particularly those quantitated as grades 1 and 2 and in lesions regarded as types 1 and 2. The greatest divergence was observed for prevalence of nodular pulmonary lesions (type 4). There was also a considerable divergence in the type 3 alteration characterized by nonnodular aggregates of carbon-laden macrophages accompanied by minimal reactive fibrosis. It appears that an objective pathological diagnosis of coal workers' pneumoconiosis (CWP) can be rendered only by the demonstration of type 4 lesions. Approximately 25% of coal miners exhibited unequivocal features of CWP. No significant differences concerning incidence or types of emphysema or frequency of chronic cor pulmonale were encountered between the two populations.

Adult↗

Fluorescence polarization with FDA in leukaemic cells: a clear difference between myelogenous and lymphocytic origins.

Intracellular fluorescence polarization (IFP) values of normal human lymphocytes and leukaemic cells from newly diagnosed patients were determined from fluorescence polarization using fluorescein diacetate (FDA). Thirty healthy donors and 40 patients with various types of leukaemia (20 myelogenous and 20 lymphocytic) were included in the present studies. The result was that myeloid cells had about twice the polarization value of lymphocytic cells. The use of FDA for the determination of IFP appears to be useful for differential diagnosis, at least between acute myelogenous and lymphocytic leukaemias. These 2 types of leukaemia also showed a pronounced difference in fluorescence intensity when treated with FDA, perhaps owing to a difference in uptake velocity. The previously described membrane microviscosity using 1,6-diphenyl-1,3,5-hexatriene (DPH), however, did not show such a difference between these 2 leukaemias. The fluorescein-binding protein(s) was also investigated in order to clarify its effect on IFP, but there seemed little evidence for the existence of any such dyebinding protein(s). The advantages of the present method, using FDA, reside in its simplicity, rapidity and considerable sensitivity, requiring a small sample of blood usually less than 5 ml.

Adolescent↗

Effect of phenobarbital, polychlorinated biphenyl and sodium saccharin on hepatic and renal carcinogenesis in unilaterally nephrectomized rats given N-ethyl-N-hydroxyethylnitrosamine orally.

The effects of phenobarbital (PB), polychlorinated biphenyl (PCB) and sodium saccharin (SS) on hepatic and renal carcinogenesis induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were examined in male F344 rats. The rats were given 0.1% EHEN in their drinking water for 2 weeks and then diet containing 0.05% PB, 0.05% PCB or 5% SS for 32 weeks. In week 3, the right kidney was removed to promote renal neoplasia. The incidence of hepatocellular carcinoma was much higher in rats given PB or PCB than in controls given EHEN alone. PB administration significantly decreased the average number of renal-cell tumors per unit area and SS reduced the numbers of early neoplastic nodules. Treatment with PCB had no effect on renal carcinogenesis. These results indicate that chemicals may have either a promotive or inhibitory effect depending on the organ.

Animals↗

Lesions of the urinary bladder epithelium in 125 autopsy cases.

One hundred and twenty five autopsy cases of macroscopically normal-appearing bladders of both sexes were examined histologically. Proliferative lesions such as Brunn's nests and cystitis glandularis, and metaplastic lesions such as columnar or cuboidal metaplasia and squamous metaplasia were commonly found and were frequently associated with lymphocytic infiltration at all ages and in both sexes. Squamous metaplasia was more common in the female than the male. Sites of predilection for these lesions were the trigone and anterior wall except for columnar or cuboidal metaplasia and dysplasia which was distributed throughout the bladder. Since these lesions were commonly found at all ages in bladders not containing neoplasia, they cannot be regarded as premalignant lesions of the bladder. Dysplasia was detected in bladders even after the 8th decade. It is not known whether these lesions are the result of chronic irritation or neoplastic stimulus.

Adult↗

Induction of gamma-glutamyl transpeptidase positive foci in rat liver by pyrolysis products of amino acids.

The activities of pyrolysis products for initiating or promoting preneoplastic lesions were tested. In experimental series I, N-2-fluorenylacetamide (2-FAA) was used as an initiator or a promoter and 3-amino-1,4-dimethyl-5H-pyrido-[4, 3-b] indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido [4, 3-b] indole (Try-P-2), 2-amino-6-methyldipyrido [1,2-a:3', 2'-d] imidazole (Glu-P-1) or 2-amino-dipyrido [1, 2-a:3', 2'] imidazole (Glu-P-2) was administered at a fixed dose and for the same period in the initiation stage or the promotion stage. Animals were subjected to partial hepatectomy or treated with carbon tetrachloride (CCl4) to increase the induction of gamma-glutamyl transpeptidase (gamma-GT) positive foci. Trp-P-1 and Glu-P-2 administered in either the initiation or promotion stage significantly increased the induction of gamma-GT positive foci (p less than 0.001). Glu-P-1 increased the induction of gamma-GT positive foci (P less than 0.001) when administered in the initiation stage but it was not effective when administered during the promotion stage. In experimental series II, animals were given a single dose of these chemicals at one of three different dose levels with partial hepatectomy and then were fed with 2-FAA and given a single dose of CCl4. Trp-P-1, Glu-P-1 and Glu-P-2 caused dose-dependent inductions of gamma-GT positive foci.

2-Acetylaminofluorene↗

Chromosomal aberrations and sister-chromatid exchanges induced by gaseous nitrogen dioxide in cultured Chinese hamster cells.

Effects of gaseous nitrogen dioxide (NO2) on chromosomal morphology of cultured Chinese hamster V79-H3 cells were investigated. Chinese hamster cells were exposed to NO2 gas in N2 gas at NO2 concentrations of 0, 5, 10, 20, 50 and 100 ppm (v/v) for 10 min at a gas flow rate of 1000 ml/min. Both chromosomal aberrations and sister-chromatid exchanges were increased depending on the NO2 concentration. The effects of sodium nitrite (NaNO2) were also examined in comparison with those of gaseous NO2, and it was found that the effects of gaseous NO2 could not be ascribed to those of nitrous acid. The gas-exposure apparatus used in this experiments seems to be useful for quantitative investigation of the effects of various gaseous materials on cultured mammalian cells or bacterial cells.

Animals↗

Resistant hepatocytes as early changes in liver induced by polycyclic aromatic hydrocarbons.

Induction of putative preneoplastic hepatocytes which are resistant to cytotoxic effect of 2-acetylaminofluorene (2-AAF) by five carcinogenic polycyclic aromatic hydrocarbons (PAH) was tested using gamma-glutamyl transpeptidase (gamma-GT) as a histochemical marker enzyme. Benzo (a) pyrene [B(a)P], 7,12-dimethylbenz(a) anthracene (7,12-DMBA), 3-methylcholanthrene (3-MC), dibenz (a,h)-anthracene [DB(a, h)A] and benzo (a) anthracene [B(a)A] were given 12 h after partial hepatectomy (PH) followed by 2-AAF and carbon tetrachloride (CCI4) feeding, a procedure developed by this laboratory. All of the five PAHs induced a signficantly increased number of gamma-GT positive foci when compared with sham-hepatectomized (SH) or vehicle control groups. The numbers of gamma-GT-positive foci induced by B(as)P, 7,12-DMBA, 3-MC and DB (a,h)A were significantly different from all of the parent compounds, anthracene, naphthalene, pyrene and phenanthrene. B(a)A did not induce significantly increased number of foci only when compared to anthracene. Possible usefulness of this system for in vivo short-term assay is discussed.

Animals↗

Chronic effects of norharman in rats treated with aniline.

The carcinogenic effects of aniline and norharman given alone or in combination were examined in rats. Neoplastic changes including hyperplastic changes of the urinary bladder were not found in all groups. Papillomas of forestomach were observed in 5 rats out of 110 rats. However, this was not significantly different among the groups. Pyelonephritis or chronic nephritis were also seen in all groups. Hematological and blood biochemical analysis did not show any notable difference in the animals treated with aniline and/or norharman.

Alkaloids↗