Search PubMed⌕ Search

Biomedical subjects

S Ozono

Publications and source records attributed to S Ozono.

156 records · Page 9Linked to original sources
PubMed1985

Agglutination by concanavalin A of urothelial cells of heterotropically transplanted rat urinary bladders: effect of bladder carcinogens and urine.

N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN) has been considered to be a carcinogenic urinary metabolite of N-butyl-N-(4-hydroxybutyl)nitrosamine. No tumor developed, however, in the heterotropically transplanted rat urinary bladders (HTBs) following repeated instillation of BCPN dissolved in physiological saline. In the present study, the possibility that BCPN dissolved in urine may induce tumors was explored using a short-term screening assay. When tested with the concanavalin A agglutination assay with which a close correlation between increase in cell agglutinability and carcinogenicity of test compounds has been well demonstrated, no significant increase in agglutinability attributable solely to BCPN was observed in HTB cells whether it was dissolved in saline or urine. Based on the current findings together with other available data, it is suggested that urothelial cells have a very limited capability to activate BCPN to the ultimate carcinogen, and require continuous contact with the carcinogen to respond with tumor formation.

Agglutination↗
PubMed1985

Inhibition of carcinogenesis by alpha-difluoromethylornithine in heterotopically transplanted rat urinary bladders.

Inhibitory effects of alpha-difluoromethylornithine (DFMO) on urinary bladder carcinogenesis were examined using the heterotopically transplanted rat urinary bladder (HTB) model. Male Fischer rats with an HTB were arbitrarily divided into four groups. Group 1 rats received into the HTBs 0.25 mg of N-methyl-N-nitrosourea (MNU) once a week for 3 weeks, followed by instillation twice a week of 0.5 ml of 2% DFMO dissolved in normal rat urine. Group 2 rats received the same amount of MNU, followed by instillation of urine without DFMO. Group 3 rats received a single dose of 0.25 mg of MNU, followed by instillation twice a week of urine containing 2% DFMO. Group 4 rats were treated as those in Group 3 but without DFMO. At 8, 14, and 20 weeks after the last MNU administration, urothelial polyamine levels and [3H] thymidine incorporation by the urothelium of HTBs were determined in nine rats of Groups 1 and 2. The remaining animals of Groups 1 and 2 were killed 25 weeks after the beginning of MNU injection, while those of Groups 3 and 4, 30 weeks after the MNU treatment. The contents of 3 polyamines (putrescine, spermidine, and spermine) in urothelial cells were significantly lower in Group 1 as compared with Group 2. The incidences of carcinoma were significantly lower in the groups treated with DFMO (p less than 0.001, Group 1 versus Group 2; p less than 0.005, Group 3 versus Group 4). These observations indicate that administration of DFMO inhibits (or retards) bladder carcinogenesis in HTBs. A possible mechanism for this effect is suppression of polyamine biosynthesis and proliferation of bladder epithelial cells.

Animals↗
PubMed1984

Diffuse papillomatosis of rat urinary bladder occurring in association with vesical calculi.

Repeated intravesical administrations of 0.9 per cent NaCl solution with or without bladder carcinogen N-butyl-N-(3-carboxypropyl)nitrosamine resulted in a high incidence of calculus formation in the urinary bladder. In all such cases, diffuse papillomatosis of the bladder urothelium was observed. "Invasion" of the tunica muscularis and the tunica adventitia by tumor was demonstrated as early as week 9 of the experiment. Morphologically, the lesions could not be distinguished from the bladder tumors induced by an orally administered carcinogen. Evidence was presented to conclude that they represent neoplasms of low malignant potential. The results indicate that bladder tumors may develop in the absence of known exposure to carcinogen provided the urothelium is chronically stimulated. Tumors solely attributable to N-butyl-N-(3-carboxypropyl)nitrosamine treatment did not occur.

Animals↗
PubMed1984

Irreversibility of low-grade superficial rat bladder carcinomas.

The present investigation was conducted to determine: (a) whether the superficial papillary tumors developing in heterotopically transplanted bladders (HTBs) of rats after N-methyl-N-nitrosourea (MNU) initiation and subsequent weekly urine treatment would regress when placed in a urine-free environment; (b) whether tumors would develop in HTBs if MNU initiation is not followed by further manipulation, such as instillation of urine or 2.1% NaCl solution; and (c) whether tumors would develop in HTBs if urine instillation is delayed for as many as 25 weeks after MNU initiation. The results indicate: (a) that low-grade superficial tumors, once developed, do not appear to regress in a urine-free environment; (b) that tumors develop in MNU-initiated bladders even if they receive no further treatment; and (c) that late institution of urine instillation to HTBs still effectively enhances MNU-initiated tumorigenesis. If the current observation is extrapolated to the human situation, our data suggest that low-grade superficial tumors are indeed neoplastic, and spontaneous regression cannot be expected by urinary diversion. It, however, might be effective in controlling progression of at least some of the early neoplastic lesions to overt cancer.

Animals↗
PubMed1984

Effects of 12-O-tetradecanoylphorbol-13-acetate on carcinogenesis in the heterotopically transplanted rat urinary bladder.

12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent promoter of mouse skin carcinogenesis, was tested for possible tumor-enhancing effects on urinary bladder carcinogenesis using the heterotopically transplanted bladder (HTB) model. Weekly administration of TPA at 1.0 microgram/week to N-methyl-N-nitrosourea-initiated HTBs did not increase tumor incidence, but instead, resulted in a significantly high incidence of nodulopapillary hyperplasia, an early neoplastic lesion, suggesting possible tumor enhancement by TPA. In addition, administration of a high dose of TPA with or without a carcinogen treatment led to the development of numerous finger-like epithelial projections on the luminal surface of the HTBs. Evidence indicates that epithelial projections are formed as a result of proliferation of intermediate cells. Whether these structures evolve into true neoplastic lesions is at present unknown.

Animals↗
PubMed1983

A minimal dose of N-methyl-N-nitrosourea carcinogenic to heterotopically transplanted rat urinary bladder.

The present investigation was conducted to determine a single dose of the carcinogen N-methyl-N-nitrosourea (MNU) which remains subcarcinogenic in a heterotopically transplanted rat urinary bladder with a communicating reservoir (HTB) either in a urine-free or urine-existing environment. A single dose of MNU, either 0.1 mg or 0.025 mg, was instilled directly into the HTB, and was followed by weekly instillation of normal rat urine or 2.1% NaCl solution (equiosmolar to the urine) for up to 52 weeks. Bladder tumors observed were divided into 2 categories depending upon their location. Those arising at the hyperplastic foci which were induced by mechanical irritation by the connector tip were referred to as inflammatory polyp (IP)-related tumors and those arising in the region free from the IP changes were referred to as IP-unrelated tumors. The results indicated that both carcinogen levels fail to induce IP-related or IP-unrelated tumors in the urine-free environment. In the presence of urine, however, the high MNU dose (0.1 mg) was tumorigenic at both IP-related and IP-unrelated sites, whereas, the low MNU dose exhibited tumorigenicity only at the IP-related site. Physical irritation by the connector enhanced MNU-initiated tumorigenesis at the connector tip only in the presence of urine in bladder lumen. Physical irritation per se induced tumors at the connector tip even without prior carcinogen treatment provided urine was present in the HTBs.

Animals↗
PubMedDate not supplied

Prognostic value of nm23 protein expression in renal cell carcinomas.

In the present study, an analysis of whether expression of nm23-H1 and nm23-H2 proteins has prognostic significance was performed. A series of 95 renal cell carcinomas was analyzed for nuclear grade, tumor size (larger than 50 mm or not), staging in the Robson system and expression of nm23-H1 and nm23-H2, as well as patient survival. Immunohistochemical staining of nm23-H1 and nm23-H2 was found in 68.4 and 50.5% of the cases, respectively. Significant differences in nm23-H1, but not nm23-H2 expression were noted with regard to nuclear grade and tumor size. The patients with nm23-H1-expression-negative tumors sized < or = 50 mm had a significantly poorer prognosis than their positive counterparts. Multivariate analysis using the Cox proportional hazards regression model indicated that the staging in the Robson system and expression of nm23-H1 were significant and independent prognostic factors for survival. However, no significant correlation between the incidence of metastasis and expression of nm23-H1 or nm23-H2 was found. The results imply that reduced expression of nm23-H1 influences the prognosis of patients with renal cell carcinomas, but not the likelihood of metastasis. In small tumors sized < or = 50 mm, reduced expression of nm23-H1 protein was suggested to be an especially strong predictor of a poor prognosis.

Adult↗
PubMedDate not supplied

Different expression of nm23-H1 and nm23-H2 protein with proliferative activities in various sizes of human renal cell carcinoma.

Ninety-five paraffin blocks of renal cell carcinomas (RCCs) and background normal tissue were obtained from patients in Nara Medical University Hospital and used for studying silver-binding nucleolar organizer regions (AgNORs), proliferating cell nuclear antigen (PCNA) and nm23 oncogenes. The RCCs were grouped by size (< or = 30, > 30 and < or = 50, > 50 mm of average diameter) and grade according to the General Rules for Clinical and Pathological Studies of Renal Cell Carcinoma, Japan. Numbers of cases were 17 in the < or = 30-mm group, 36 in the > 30- and < or = 50-mm group, and 42 in the > 50-mm group. AgNOR scores were 4.68 +/- 1.22, 3.91 +/- 1.31 and 3.01 +/- 1.05, respectively, with significant intergroup differences. Frequencies of PCNA-positive cells per 500 cells were 33.8 +/- 23.5, 39.4 +/- 13.8 and 45.9 +/- 38.8. nm23-H1 immunohistochemical staining proved strongly positive in 21 of 24 areas of normal proximal convoluted tubules, 4 of 8 dysplasia cases, 2 of 17 in the < or = 30-mm group RCCs, 1 of 36 in the > 30- and < or = 50-mm group RCCs and none of 42 in the > 50-mm RCCs. nm23-H2 in contrast was weakly positive in 3/24, 2/8, 12/17, 30/36 and 20/42 of the cases, respectively. The results indicated an inverse relationship between tumor size and score of AgNOR without any variation in PCNA labeling and contrasting expression of nm23-H1 and nm23-H2 linked to the size of RCCs.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Experimental model of renal tumors in polycystic kidneys: effects of long-term 2-amino-4,5-diphenylthiazole administration in rats treated with N-ethyl-N-hydroxyethylnitrosamine.

We previously reported that treatment of Fischer-344 rats with 2-amino-4,5-diphenylthiazole (DPT) results in renal cystic changes. The present study was undertaken to examine the effects of long-term DPT treatment after initiation of kidney carcinogenesis with N-ethyl-N-hydroxyethylnitrosoamine (EHEN) in Wistar rats. One hundred forty-four 6-wk-old male Wistar rats were divided into 6 equal receiving groups: 1000 ppm EHEN or normal tap water for 2 wk followed by 1.06% DPT or basal diet for the subsequent 14 or 30 wk. Controls were maintained without treatment throughout. Subgroups of 6 animals from each group were sacrificed after 8, 16, 24, and 32 wk for histopathological assessment of lesion development in the kidneys and liver. Animals treated with DPT first developed cystic changes of the kidneys (primarily at the corticomedullary border) after 8 wk of treatment, and these changes progressed with time thereafter. In the groups in which DPT treatment was discontinued after 14 wk, cysts then gradually decreased in size. All tumors detected in the kidneys were histopathologically diagnosed as renal cell adenomas. The tumor multiplicity after 32 wk of treatment was significantly higher in Group I, receiving EHEN + DPT for 30 wk (6.33 +/- 4.46), and Group III, receiving EHEN + DPT for 14 wk (3.83 +/- 1.57), than in Group V, EHEN alone (1.00 +/- 0.58) (p < 0.05). Renal cell tumors within cysts were only seen in Groups I and III. The general bromodeoxyuridine labeling indices for the kidneys at week 32 were significantly higher in Group I (55.94 +/- 21.08 cells/mm2) and Group III (53.75 +/- 12.38 cells/mm2) than in Group V (22.38 +/- 6.98 cells/mm2) (p < 0.05). In conclusion, DPT caused cystic changes in rat kidneys, which, however, gradually decreased in size after the treatment was discontinued, suggesting a reversible nature. DPT clearly also promotes renal tumor development after EHEN initiation, and this effect persists, to a certain extent, even after the insult is removed.

Animals↗
PubMedDate not supplied

Effect of hexachloro-1,3-butadiene on renal carcinogenesis in male rats pretreated with N-ethyl-N-hydroxyethylnitrosamine.

Hexachloro-1,3-butadiene (HCBD) is a potent nephrotoxicant that selectively damages the straight portion (pars recta) of the proximal tubule in the rat. To determine its effects on carcinogenesis. HCBD was administered for 30 wk at a concentration of 0.1% by weight in basal diet to male Wistar rats previously given 0.1% N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the drinking water for 2 wk. The combined treatment resulted in a significantly higher incidence of renal cell tumors than when EHEN was administered alone. This chronic exposure and a short course of a 0.2% HCBD diet for 3 wk caused marked increase in the numbers of bromodeoxyuridine-incorporating cells or proliferating cell nuclear antigen-positive cells in the outer stripe of the kidney. The ability of HCBD to promote EHEN-initiated renal tumorigenesis in rats thus appears to be associated intimately with linked nephropathy and subsequent cell proliferation.

Adenoma↗