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Biomedical subjects

T Kokubo

Publications and source records attributed to T Kokubo.

At least 325 records · Page 18Linked to original sources
PubMed1984

Carcinogenicity of low doses of N-ethyl-N-nitrosourea in F344 rats; a dose-response study.

The threshold level of minimum carcinogenic dose of N-ethyl-N-nitrosourea (ENU) and the effect of dose on organ specificity were examined by continuous oral administration to both sexes of F344 rats of low doses of ENU at four concentrations (0.3, 1, 3 and 10 ppm) in the drinking water. ENU at 10 ppm selectively induced neurogenic tumors and tumors of the digestive tract, including duodenal tumors. Even at lower doses it enhanced the spontaneous development of some other tumors. A high dose of ENU (400 ppm) was previously found to induce duodenal tumors selectively. These results indicate that the organ specificity of ENU is influenced by the dose and that ENU has multi-potent carcinogenic activity in many organs and/or tissues. In this study, some specific tumors, such as those of the nervous system and digestive tract, seemed to require a minimum carcinogenic level of ENU (10 ppm) for their appearance. However, it seems that ENU is carcinogenic at much lower dose levels than 10 ppm because ENU enhanced the spontaneous development of some other tumors in many experimental groups. The so-called virtually safe doses inducing these specific tumors at a risk level of 10(-6) were calculated.

Animals↗
PubMed1983

Effect of dibutyltin dichloride on incidence of pancreatic adenocarcinoma induced in hamsters by a single dose of N-nitrosobis(2-oxopropyl)amine.

The effects of timing of a single intragastric application of dibutyltin dichloride, at a dosage of 30 mg/kg body wt, on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas have been studied in female Syrian golden hamsters. Dibutyltin dichloride, which has been shown to produce selected bile duct injury, was administered either 1 week before or 1 week after a single injection of BOP (20 mg/kg body wt). Control hamsters were injected with BOP alone or were given dibutyltin dichloride alone. The incidence of ductal adenocarcinomas strikingly decreased in hamsters when dibutyltin dichloride was ingested after BOP treatment, but remained unaffected when dibutyltin dichloride was given before carcinogen treatment. Two cases of sarcoma were observed in the group treated with dibutyltin dichloride before BOP injection. The incidence of insulomas, which were considered as spontaneous tumors, was not influenced by dibutyltin dichloride. These results showed that intragastric application of dibutyltin dichloride after BOP treatment significantly reduced the induction of pancreatic cancer. These findings do not support speculations based on epidemiologic studies as to a promoting effect of cholestasis.

Animals↗
PubMed1983

Carcinogenicity of potassium bromate administered orally to F344 rats.

The carcinogenicity of potassium bromate, a food additive and a neutralizer in permanent waving, was tested by adding it to the drinking water of F344 rats for 110 weeks. Groups of 53 males and 53 females, each, were given solutions of 500 or 250 ppm of potassium bromate or distilled water. A concentration of 500 ppm markedly inhibited an increase of body weight of male rats. The mean survival time was shortest for males given 500 ppm (88.1 +/- 18.1 wk); the survival times of other groups were 101-104 weeks. The percentage survival in week 104 was relatively high in all groups, and it was 77.4% for males and 66.0% for females in the control group. High incidences of renal cell tumors (in males and females given 500 or 250 ppm) and mesotheliomas of the peritoneum (in males given 500 ppm) were observed. The incidences of these tumors in test groups were significantly higher than those in controls (P less than .001). It was concluded that, when orally administered under the conditions of this experiment, potassium bromate was carcinogenic to F344 rats.

Adenocarcinoma↗
PubMed1983

Enhancement by potassium bromate of renal tumorigenesis initiated by N-ethyl-N-hydroxyethylnitrosamine in F-344 rats.

The effect of potassium bromate, a food additive, was examined in male F-344 rats based on two-stage renal carcinogenesis with N-ethyl-N-hydroxyethylnitrosamine (EHEN) as an initiator. Average numbers of dysplastic foci and renal cell tumors were significantly increased in rats given potassium bromate after initiation with EHEN. It was concluded that potassium bromate has an enhancing effect on renal tumorigenesis.

Animals↗
PubMed1983

Long-term in vivo carcinogenicity test of fish meal pyrolysate in Syrian golden hamsters.

The carcinogenicity of fish meal pyrolysate was examined in noninbred Syrian golden hamsters of both sexes. Hamsters were given a diet containing 5%, 10%, 20% or 40% fish meal pyrolysate for 102 weeks in Experiment 1, and 10% or 20% fish meal pyrolysate for 112 weeks in Experiment 2. Hamsters in control groups in both experiments were fed a normal basal diet. Various tumors were found in both experimental and corresponding control groups, but there was no significant difference in the incidence of any tumors between the experimental and control groups. Thus, the fish meal pyrolysate tested was not carcinogenic to Syrian golden hamsters under these conditions. In male hamsters the severity and incidence of fatty degeneration of the liver and chronic nephropathy tended to correlate with the concentration of fish meal pyrolysate in the diet. With females, however, the correlation was not so clear. In neither sex did the presence of atrial thrombosis or systemic amyloidosis appear to be dependent on the dietary concentration of fish meal pyrolysate.

Amyloidosis↗
PubMed1983

Effect of high salt diet on rat gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.

The influence of sodium chloride on chemical carcinogenesis of the gastroduodenal tract was examined in male outbred Wistar rats exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/liter) for 20 weeks. Sodium chloride given concomitantly with MNNG during the first 20 weeks of the experiment increased both the incidence and the size of tumors at 40 weeks. However, sodium chloride given after MNNG during the second 20 weeks of the experiment did not enhance tumor development. This study indicates that, although sodium chloride given with MNNG enhances tumor development, sodium chloride does not promote gastric carcinogenesis.

Animals↗
PubMed1983

Spontaneous tumors in F-344/DuCrj rats.

Spontaneous tumors in 296 male and 297 female F-34/DuCrj rats used as control groups in six carcinogenicity tests were tabulated and evaluated. In males the most frequent tumors were testicular interstitial cell tumors, followed by mammary fibromas and fibroadenomas, mononuclear cell leukemias, pheochromocytomas, C-cell adenomas of the thyroid, pituitary adenomas, preputial adenomas, neoplastic nodules of the liver, and lung adenomas. In contrast, in females pituitary adenomas, uterine endometrial stromal polyps, mammary fibroadenomas, mononuclear cell leukemias and C-cell adenomas were the most common. Various other tumors of almost all other organs and/or tissues were found, although their incidences were low. Variability in the rates of incidence in some tumors was observed in different control groups.

Age Factors↗
PubMed1982

Carcinogenicity of alpha-oxidized nitrosamines (alpha-acyloxy, alpha-hydroperoxy, and alpha-oxo nitrosamines) in F-344 rats.

The carcinogenicity of eleven alpha-oxidized nitrosamines (alpha-acyloxy, alpha-hydroperoxy and alpha-oxo nitrosamines) was tested in F-344 rats. All chemicals were dissolved in olive oil and rats received 10 weekly subcutaneous injections of these chemicals (10 x 5 mg/kg of N-methyl-N-(acetoxymethyl) nitrosamine or equimolar amounts of the other chemicals) at the interscapular region. Subcutaneous tumours were detected in many rats of all groups treated with the chemicals, although no tumour was detected at the injection site in the control group. Lung and thyroid tumours were also observed in many rats of the treated groups, especially those injected with N-alkyl-N-(acetoxymethyl)nitrosamines. Many other tumours developed in the experimental groups, but it is not certain that they were related to the treatment with the chemicals. The results indicate that the chemicals possess local as well as systemic carcinogenicity in F-344 rats. The potent carcinogenic effects at the injection site of the alpha-oxidized nitrosamines, coupled with their direct mutagenic activity, suggest that these derivatives are useful models for the ultimate form of the metabolically activated nitrosamines.

Animals↗
PubMed1982

Vascular tumors of the spleen and other neoplasms induced in Syrian golden hamsters by 1-propyl-1-nitrosourea.

Continuous administration of either 400 ppm or 100 ppm 1-propyl-1-nitrosourea (PNU) in drinking water to Syrian golden hamsters, from 11 weeks of age, induced tumors of the spleen, forestomach, duodenum, and vagina. The tumor incidences in the spleen were 33 of the 36 males (91.7%) and 34 of the 37 females (91.9%) in the 400 ppm group and 32 of the 40 males (80%) and 26 of the 34 females (76.5%) in the 100 ppm group. In addition, tumors were induced in the forestomach and duodenum of both sexes and in the vagina in females. Histologically, the tumors were classified as hemangioendotheliomas of the spleen, squamous cell papillomas and carcinomas of the forestomach, adenocarcinomas of the duodenum, and squamous cell papillomas and carcinomas of the vagina. Compared to results previously reported in rats, the present results reveal a remarkable species difference in the organ specificity of PNU.

Adenocarcinoma↗
PubMed1981

Preservation of gastric gland character in transplantable gastric adenocarcinoma (SG2B) of rats.

The morphological and biochemical characteristics of a transplantable tumor line of rat gastric carcinoma (SG2B), that developed in a Wistar strain rat after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and then 4-nitro-quinoline 1-oxide were examined at the 60th passage. The tumor was serially transplanted into newborn rats by subcutaneous and intraperitoneal routes and has been passed through 60 transplant generations over a 4-year period. The tumors appeared to be well-differentiated tubular adenocarcinomas throughout successive passages, and at each generation transplants were almost identical to the original gastric adenocarcinoma as judged by light and electron microscopic observation. Ultrastructurally, the neoplastic cell contained abundant free ribosomes and exhibited few mucin granules. The microville on the apical cell surface were short and irregularly spaced. Electrophoresis showed that pepsinogens (Pg) 3 and 4 were present but no Pg 1 was detectable at the 60th passage, as was the case in the tissue at the 2nd and 5th passages. The pepsinogen content of the tissue at the 60th passage was similar to that at the 5th passage. The tumor tissue has thus retained the morphological and biochemical character of a pyloric gland type tumor for a long time (over 4 years) during serial transplantation.

4-Nitroquinoline-1-oxide↗
PubMed1981

Changes of amylase during experimental pancreatic carcinogenesis in hamsters.

Changes of amylase activity and isozymic pattern in the serum, urine, ascites, pancreas and parotid gland of hamsters during pancreatic carcinogenesis induced by N-nitrosobis (2-oxopropyl) amine (BOP) were examined. During the early stage of pancreatic carcinogenesis, amylase activity in the urine was greatly increased and the pancreatic type of isozyme increased in the serum and urine, but in the terminal stage, the activity decreased and the isozymic pattern reverted to normal. These alterations of amylase could be due to focal pancreatitis around dysplastic ductules and small carcinoma lesions causing leakage of pancreatic juice. This phenomenon may be of value in diagnosis of the early stage of pancreatic cancer.

Adenocarcinoma↗
PubMed1981

Ulcer formation and associated tumor production in multiple sites within the stomach and duodenum of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.

The effect of ulcers on the development of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine in (MNNG) was studied in male Wistar rats. Ulcers were produced by the application of a steel rod, 5 mm in diameter and frozen at -78 degrees C, to the serosal surface of the forestomach, fundus, pylorus, or proximal duodenum. The existence of the ulcers at these areas was confirmed 1 week later in a preliminary experiment. Experimental groups were given MNNG in their drinking water at a concentration of 100 micrograms/ml for 16 weeks beginning 7 days after the ulcers developed. Administration of MNNG after ulceration resulted in a relative increase in the tumor incidences at each ulcer site, especially the proximal duodenum, which suggested that regenerating cells in the duodenum were the most susceptible cells among the cells of the four sites. The increase in tumor incidence following ulceration may be due to exposure of MNNG to a greater number of regenerating cells during the renewal process that seem to be more responsive to carcinogenic influences that normal cells.

Adenocarcinoma↗