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T Masui

Publications and source records attributed to T Masui.

At least 127 records · Page 7Linked to original sources
PubMed1988

Summation effect of uracil on the two-stage and multistage models of urinary bladder carcinogenesis in F344 rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Uracil is known to cause reversible urolithiasis and to induce papillomatosis in the urinary bladder of F344 rats. We examined whether the marked urothelial cell proliferation caused by uracil, given in the middle of the post-initiation stages, enhances the promoting activity of a promoter in the two-stage model or the promoting and/or carcinogenic activity of a low-dose carcinogen in the multistage model of urinary bladder carcinogenesis. Rats were initiated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks, and then 2% butylated hydroxyanisole (BHA) or 0.002% N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) were given during experimental weeks 4-9 and weeks 12-20. Uracil was given during weeks 9-12 at a level of 3% of the diet. Rats in the control group were treated with BBN and uracil. Rats were killed at weeks 16 and 20. At week 16, higher occurrences of papillary or nodular (PN) hyperplasia and papilloma were observed in uracil-BHA-treated rats than in the controls. At week 20, significantly higher incidences of PN hyperplasia and papilloma were observed in both uracil-EHBN- and uracil-BHA-treated groups, and a summation effect of uracil was observed. These results indicate that uracil given in the middle of the post-initiation stage enhanced the promoting activity of the compound through marked proliferation of the bladder epithelium.

Animals↗
PubMed1988

Genomic 5-methyldeoxycytidine decreases associated with the induction of squamous differentiation in cultured normal human bronchial epithelial cells.

The terminal squamous differentiation of epithelial cells involves a number of cellular changes. However, the mechanisms underlying this differentiation process are unknown. The present study demonstrates that 5-azacytidine, 12-O-tetradecanoylphorbol-13-acetate (TPA) and type beta-transforming growth factor (TGF-beta) significantly diminish the genomic 5-methyldeoxycytidine (5mdC) content of normal human bronchial epithelial cells concomitantly with the induction of squamous differentiation. 5-Azacytidine or TPA, but not type beta-transforming growth factor, also initiated decreases in the genomic 5mdC content of differentiation nonresponsive human tumor A549 cells. These effects of TPA or type beta-transforming growth factor occurred at concentrations of 1 nM and 1.2 pM, respectively, which were approximately one tenth of kd values of their specific receptors. Therefore, the decreases in genomic 5mdC induced by these agents were probably mediated, directly or indirectly, by receptor--ligand interactions.

Azacitidine↗
PubMed1988

Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S-transferase placental form positive foci in rats--an approach for a new medium-term bioassay system.

A large series of assays of the hepatocarcinogenic potential of 112 different compounds were carried out using a rapid bioassay system developed in this laboratory based on the two-step concept of hepatocarcinogenesis. 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 killed, all rats being subjected to two-thirds partial hepatectomy (PH) at week 3. Carcinogenic potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive (GST-P+) foci in the liver with those of the corresponding control group given DEN alone. Positive was scored for a significant increase in the value of GST-P+ foci, negative for no change or a decrease. Results were compared to reported Salmonella/microsome and long-term carcinogenicity test findings. Of the liver carcinogens, 10 out of 11 (90.9%) mutagenic, and 11 out of 13 (84.6%) non-mutagenic compounds gave positive results (mean, 87.5%). Carcinogens other than the hepatocarcinogens gave less positive results (two out of 17, 11.8%). None of the compounds reported as non-carcinogenic demonstrated positivity suggesting that the assay system does not suffer from the disadvantage of false-positive results. The protocol system also provided information concerning the inhibitory potential of compounds such as anti-oxidants. It is concluded that the present experimental protocol which requires far fewer animals and shorter duration than a long-term carcinogenicity test has practical applications for the rapid and economical screening of environmental hepatocarcinogens and their inhibitory agents.

Animals↗
PubMed1988

Effects of sodium L-ascorbate, uracil, butylated hydroxyanisole and extracellular pH on junctional intercellular communication of BALB/c 3T3 cells.

To study the mechanism of tumor promotion by different classes of urinary bladder promoters, the effect of sodium L-ascorbate, uracil and butylated hydroxyanisole (BHA) on junctional intercellular communication was examined in cultured BALB/c 3T3 cells using a dye-transfer method. In addition, since administration of sodium L-ascorbate and several other bladder tumor promoters is known to result in increased urinary pH, the effect of pH of the culture medium on intercellular communication was investigated. Results showed that under the present experimental conditions on the BALB/c 3T3 cells, BHA inhibited intercellular communication while sodium L-ascorbate and uracil did not. Intercellular communication was inhibited in proportion to the increase of medium pH after incubation of 4 h. Although further study is necessary to confirm the negative results of sodium L-ascorbate and uracil, these results suggest differences in the promoting mechanism(s) among these agents.

Animals↗
PubMed1988

Uracil-induced calculi and proliferative lesions of the mouse urinary bladder.

Uracil fed as 3% of the diet to rats produces urinary calculi and consequent proliferative lesions of the bladder epithelium, including papillomatosis. We evaluated the effects of dietary uracil in two strains of mice and compared the results in males and females. Uracil was fed as 3 or 1% of the diet to male and female Swiss and C3H mice for up to 20 weeks. The 3% dose produced marked proliferative changes in the bladder epithelium by 10 weeks of administration, the earliest time at which the animals were processed for microscopic evaluation. These lesions progressed to severe nodular and papillary hyperplasia so that all of the animals fed 3% uracil had to be killed by the end of the 15th week. These animals had uracil-formed calculi. In contrast, mice fed 1% uracil rarely developed uracil calculi, and also rarely developed proliferative changes in the bladder epithelium as observed by light microscopy. Also, the labeling index was determined and showed quantitatively the degree of cell proliferation similar to that qualitatively observed by light microscopic examination. At 10 weeks of administration, there was an increased labeling index in the males compared to females in both strains of mice fed 3% uracil, but this difference was not significant at 15 weeks. Similarly, the males tended to have more severe histologic changes than the females. The results of feeding high doses of uracil are similar in mice to those previously observed in rats.

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

Condyloma acuminatum of the bladder in two autopsy cases.

Condyloma acuminatum is a very rare lesion occurring in the bladder. We report two cases of condyloma acuminatum of the bladder found at autopsy, one in a 96-year-old woman and the other in an 80-year-old man. Both had papillary or polypoid tumorous lesions in the trigone and neck of the bladder. The lesions were composed of nodular or papillary growths of squamous epithelium. The epithelium exhibited koilocytosis and the nuclei showed immunohistochemical staining for human papillomavirus antigen.

Aged↗
PubMed1987

High-performance liquid chromatographic determination of six p-hydroxybenzoic acid esters in cosmetics using Sep-Pak florisil cartridges for sample pre-treatment.

A rapid and simple method is described for the simultaneous determination of methyl, ethyl, isopropyl, n-propyl, isobutyl and n-butyl p-hydroxybenzoic acid esters (parabens) in cosmetics by high-performance liquid chromatography (HPLC). The method involves a single extraction of parabens with diethyl ether and clean-up on a Sep-Pak Florisil cartridge. Fat-soluble excipients in the diethyl ether extracts are removed through the cartridges with hexane-chloroform (75:25). Parabens are then eluted from the cartridges with hexane-ethyl acetate (70:30) and determined by HPLC on a reversed-phase column with water-methanol (50:50) as the mobile phase using sec.-butylpraben as an internal standard. The method was applied to samples with complicated matrices such as cream, milk lotion, lotion and cleansing foam, and the recoveries were 99.0-102.3% with coefficients of variation of 0.3-1.2%.

Chromatography, High Pressure Liquid↗
PubMed1987

Compared promoting potential of D-galactosamine, carbon tetrachloride and partial hepatectomy in rapid induction of preneoplastic liver lesions in the rat.

Effectiveness of two different chemically induced stimuli for hepatocellular proliferation was compared with regard to that of commonly used partial hepatectomy (PH), for the purpose of developing short-term protocol for the assay of promoting agents of hepatocarcinogenesis. Enhancing effect of D-galactosamine (DGA) and carbon tetrachloride (CCl4) given during the promotion procedure by 2-acetylaminofluorene (2-AAF) was compared along with PH in rats initiated by diethylnitrosamine (DEN), using preneoplastic glutathione S-transferase positive (GST-P+) hepatocyte foci as an end-point marker lesion. The number of GST-P+ foci per cm2 was largest in the group given CCl4 followed by DGA, no treatment (2-AAF alone) and PH. In contrast, the area (mm2) per cm2 and mean diameter of the focus were largest in the PH group then DGA followed by CCl4 and no treatment. The results indicate that the number of GST-P+ foci were not clearly affected by 3 different treatments whereas area and size of foci which represented the result of promoting effect were clearly influenced by those treatments, indicating they caused differential proliferation of initiated cells. In this respect, even though PH is the most potent procedure, DGA is also efficient and preferred to CCl4 for the non-surgical enhancing method.

Animals↗
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

Preneoplastic and neoplastic growth of xenotransplanted lung-derived human cell lines using deepithelialized rat tracheas.

The human lung tumor-derived cell lines A549, Calu-1, Calu-3, HuT292, and SW900 and the transformed human bronchial epithelial cell line TBE-1, that was transfected with the v-Harvey-ras oncogene, were inoculated into deepithelialized Fisher 344 rat tracheas (5 X 10(5) cells/trachea). After the ends of the tracheas were sealed, the tracheas were transplanted into s.c. tissues of nude mice. In a parallel experiment, 1 X 10(6) cells from each of these cell lines were injected s.c. Histological examination of the tracheal transplants 2, 4, 8, 12, and 16 weeks after cell inoculation proved to be of greater usefulness than either clinical or histological observation of the s.c. injection sites. A549, Calu-1, and TBE-1 produced intratracheal neoplastic nodules as early as 2 weeks after cell inoculation. Calu-3, HuT292, and SW900 grew relatively slowly in the tracheas, and simple or stratified epithelia with slight or moderate atypia (preneoplastic lesions) were seen at 2 weeks. After the 4th week, they produced tumor nodules in the tracheal transplants, whereas no tumor cells could be seen at the s.c. injection sites. The human derivation of the cells was confirmed by in situ hybridization using human-specific DNA probes. The intratracheal inoculation and xenotransplantation of human-derived cell lines offers a time-saving alternative to the s.c. inoculation assay for tumorigenicity and is at the same time a potentially valuable approach to studying preneoplastic and neoplastic progression with human cell subpopulations.

Animals↗
PubMed1987

Distribution and modulation of the cellular receptor for transforming growth factor-beta.

Scatchard analyses of the binding of transforming growth factor-beta (TGF-beta) to a wide variety of different cell types in culture revealed the universal presence of high affinity (Kd = 1-60 pM) receptors for TGF-beta on every cell type assayed, indicating a wide potential target range for TGF-beta action. There was a strong (r = +0.85) inverse relationship between the receptor affinity and the number of receptors expressed per cell, such that at low TGF-beta concentrations, essentially all cells bound a similar number of TGF-beta molecules per cell. The binding of TGF-beta to various cell types was not altered by many agents that affect the cellular response to TGF-beta, suggesting that modulation of TGF-beta binding to its receptor may not be a primary control mechanism in TGF-beta action. Similarly, in vitro transformation resulted in only relatively small changes in the cellular binding of TGF-beta, and for those cell types that exhibited ligand-induced down-regulation of the receptor, down-regulation was not extensive. Thus the strong conservation of binding observed between cell types is also seen within a given cell type under a variety of conditions, and receptor expression appears to be essentially constitutive. Finally, the biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine TGF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro. It is proposed that this may prevent premature interaction of autocrine ligand and receptor in the Golgi apparatus.

Animals↗
PubMed1987

Inhibition of neoplastic development in rat liver, kidney, oesophagus and forestomach by 4,4'-diaminodiphenylmethane administration.

The modifying effects of 4,4'-diaminodiphenylmethane (DDPM) (0.1% in diet) administration on liver carcinogenesis induced by 2-acetylaminofluorene (2-AAF) (0.02% in diet), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) ( 0.06% in diet), diethylnitrosamine (DEN) (0.001% in drinking water) and N-ethyl-N-hydroxyethylnitrosamine (EHEN) (0.1% in drinking water), EHEN-induced oesophagus and kidney carcinogenesis and forestomach carcinogenesis induced by butylated hydroxyanisole (1.0% in diet) were examined in F344 male rats. Mean survival time tended to be longer in DDPM-supplemented groups, the difference being significant in DEN + DDPM and EHEN + DDPM groups. Intake of carcinogens was slightly but not significantly reduced by DDPM. The incidences of hyperplastic nodules and hepatocellular carcinomas were significantly decreased in 2-AAF or 3'-Me-DAB + DDPM groups. Pulmonary metastases were also less common in 3'-Me-DAB or EHEN + DDPM groups. Development of papillomas in the oesophagus but not in tumours in the forestomach was also inhibited by DDPM. Inhibition in the different organs was not significantly related to decrease in body weight or carcinogen intake, indicating a mechanism independent of non-specific toxic effects or reduction in food consumption. Some other factors possibly related to its ability to cause bile duct proliferation and/or altered activity of enzymes relevant to drug metabolism may be involved.

2-Acetylaminofluorene↗
PubMed1987

Placental glutathione S-transferase (GST-P) as a new marker for hepatocarcinogenesis: in vivo short-term screening for hepatocarcinogens.

Our laboratory has developed an in vivo short-term screening test for hepatocarcinogens based on quantitation of gamma-glutamyl transpeptidase (gamma-GT) positive foci. However, gamma-GT positive hepatocytes appear in periportal areas under a variety of circumstances apparently unrelated to hepatocarcinogenesis. Glutathione S-transferase placental type (GST-P), which is hardly detectable in normal rat liver, was recently demonstrated as a new marker protein for preneoplastic liver foci. In experiment I, rats were initially given a single dose (200 mg/kg) of diethylnitrosamine intraperitoneally and 2 weeks later were treated with test compounds for 6 weeks. All rats were subjected to partial hepatectomy at week 3. The long-term development of preneoplastic lesions was followed in rats for 50 weeks. The immunohistochemical investigation of GST-P binding and the histochemical demonstration of gamma-GT in serial sections revealed that almost all gamma-GT foci were GST-P positive, but 5-10% of GST-P foci could not be detected by gamma-GT staining. From week 8, many gamma-GT foci partially lost gamma-GT activity. However, no comparable disappearance of GST-P was evident in the lesions. All hepatocellular carcinomas (HC) found at week 50 consisted of GST-P positive HC cells. In contrast, 37.9% (11/29) of HC were negative for gamma-GT. In experiment II (in vivo short-term screening test for hepatocarcinogens), rats were treated in the same manner as for experiment I and killed at week 8. Fifty-eight chemicals were investigated for their potential to modify GST-P positive foci development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Differential modification of development of preneoplastic lesions in the Syrian golden hamster initiated with a single dose of 2,2'-dioxo-N-nitrosodipropylamine: influence of subsequent butylated hydroxyanisole, alpha-tocopherol, or carbazole.

The effects of butylated hydroxyanisole [(BHA) CAS: 25013-16-5], alpha-tocopherol [(TC) CAS: 59-02-9], and carbazole [(CA) CAS: 86-74-8] administered subsequent to a single dose of 2,2'-dioxo-N-nitrosodipropylamine [(DOPN) CAS: 60599-38-4] on the development of putative preneoplastic lesions were investigated in Syrian golden hamsters. Whereas the 2 antioxidants BHA and TC inhibited the incidence of both liver and pancreatic lesions, CA, itself giving rise to considerable numbers of enzyme-altered foci, enhanced carcinogenesis in the liver while inhibiting carcinogenesis in the pancreas. All 3 of these agents induced hyperplastic and papillomatous lesions in the forestomachs of treated animals, independent of prior DOPN treatment; these forestomach lesions were not evident in controls. Cellular atypia and invasive growth characteristics signifying malignant change were also observed in BHA-induced forestomach lesions. The results demonstrate that hepatocarcinogenesis in the Syrian golden hamster, like that in the rat, can be inhibited by antioxidants. The similar decrease in putative preneoplastic lesion yield evident in the pancreas of BHA- or TC-treated hamsters, considered in the light of similarities in altered enzyme phenotype in carcinogen-induced lesions of both organs, suggests that common biochemical changes can be an underlying factor in the modification of neoplastic development in liver and pancreas. The present results also provide further evidence that CA has carcinogenic potential for the liver and forestomach of experimental animals.

Animals↗
PubMed1987

[A case of renal cell carcinoma with the complication of a giant cyst difficult to distinguish from xanthoma].

A case of renal cell carcinoma accompanied by a giant cyst in a 69-year-old male patient is reported. The patient consulted a physician in our Hospital for bellyache on the left abdomen. Because giant cyst in the left kidney and intracystic hemorrhage were suspected by computed tomography diagnosis, the patient was transferred to the Department of Urology, As a tumor-like mass was detected in the cyst by ultrasound echo diagnosis, transperitoneal extirpation of the left kidney was conducted on May 8, 1985. At operation, a giant unilocular cyst covered with hypertrophic fibrous capsule including much coagula was observed. The inner wall of the cyst was covered with many deeply yellow torous lesions of sizes ranging from those of a wheat grain to thumb. Histologically, the lesions consisted of a cell group supposedly of histiocyte origin accompanied by cellular infiltration of lymph cells, and xanthoma was deeply suspected. However, as it was difficult to distinguish from the clear cell subtype of renal cell carcinoma, examination by an electron microscope was conducted and the final diagnosis of renal cell carcinoma was made. The post-operative course of the patient was good and no recurrence or cancer metastasis was observed as of January, 1986.

Aged↗