Biomedical subjects

J Kanno

Publications and source records attributed to J Kanno.

At least 37 records · Page 2Linked to original sources

PubMed1992

Tumor-promoting effects of both iodine deficiency and iodine excess in the rat thyroid.

Thyroid tumor-promoting effects of iodine deficiency and iodine excess were investigated in a rodent 2-stage model to estimate an optimal iodine intake range that would not effectively promote development of thyroid neoplasia. Six-week-old male F344 rats were given a single subcutaneous injection of 2,800 mg/kg body weight N-bis(2-hydroxypropyl)-nitrosamine (DHPN) or saline vehicle, maintained on Remington's iodine-deficient diet (21 +/- 2 ng/g iodide), and supplemented with various amounts of potassium iodide up to 260 mg/liter in drinking water to generate conditions ranging from severe iodine deficiency to severe iodine excess. In DHPN-treated rats, both conditions significantly increased thyroid follicular tumorigenesis. In DHPN-untreated rats, iodine deficiency produced diffuse thyroid hyperplasia, characterized by small follicles with tall epithelium and reduced colloid, together with a decrease in thyroxine (T4) and an increase in thyroid-stimulating hormone (TSH). On the other hand, iodine excess produced colloid goiter, characterized by large follicles with flat epithelium and abundant colloid admixed with normal or small-sized follicles lined by epithelium of normal height, together with normal serum T4 and slightly decreased TSH. These effects were directly proportional to the severity of iodine deficiency or extent of iodine excess and suggest that each condition has a different thyroid tumor promotion mechanism. Iodine intakes that showed the least tumor promotion were 2.6 and 9.7 micrograms/rat/day in this study. Promoting mechanisms and the problem of statistically estimating recommended daily iodine intake range are briefly discussed.

Animals↗

PubMed1992

Clinical pathology testing regulatory concerns.

In toxicity testing, each animal may have to be viewed as a surrogate for millions of people and should be examined as thoroughly as a human patient. However, there are many differences between human diagnosis and animal toxicity testing. Human diagnosis is primarily based on anamnesis, symptoms, and utilization of a huge database of diseases. However, in animal toxicity testing, clinical and anatomical pathology data are usually a primary source of toxicity information, even though the positive endpoints are generally not known in advance and the number of positive toxicity endpoints may be numerous. This situation will generate at least 2 practical problems in clinical pathology testing: (1) how to preselect test items without precise knowledge of toxicity endpoints and (2) how to handle multiple data sets for toxicity detection. The latter includes issues of inflation of the overall false-positive rate and multicomparison problems. A "disease" called "significantosis" and a concept of integrated interpretation of multiple biologically related items to avoid false-positive judgments and unnecessary censoring of meaningful outlier data are briefly discussed. In general, toxicity tests are quite exploratory and the endpoints are unknown and multiple, so the procedures for data interpretation should be determined on a case-by-case basis. Construction of toxicity entity-oriented databases may be a requirement for further refinement of toxicity study interpretation.

Animals↗

PubMed1991

Neoplastic argentaffin cells with intracytoplasmic eosinophilic granules in a gastric adenocarcinoma.

A case of poorly differentiated adenocarcinoma of the stomach with unique histological features is reported: in addition to characteristic adenocarcinoma cells, a large number of tumor cells contained bright eosinophilic and argentaffin granules in their cytoplasm. On routine histologic examination, the latter cells closely resembled the endocrine cells present in the normal human gastrointestinal tract, although the granules were distributed throughout the cytoplasm and did not show any polarity, which is usually subnuclear in normal endocrine cells. Immunohistochemical studies demonstrated positive staining for lysozyme, CEA, gastrin and HCG. Electron microscopic examination revealed cytoplasmic neurosecretory granules, and some tumor cells were found to contain both secretory granules and mucinous material within the same cytoplasm. These neoplastic endocrine cells presumably originated from primitive digestive system elements capable of differentiating towards both endocrine and mucus-secreting varieties.

Adenocarcinoma↗

PubMed1990

Melanocytes and melanosis of the oesophagus in Japanese subjects--analysis of factors effecting their increase.

Normal oesophagus specimens taken from 65 autopsy cases and surgical specimens from 127 oesophageal carcinoma cases were examined histopathologically to determine melanocyte incidence and distribution. Melanocytes were found in the epithelio-stromal junction in 7.7% of normal oesophagus specimens examined at autopsy, and in 29.9% of surgical cases with oesophageal carcinoma. Positive specimens in the latter groups, especially from pre-operatively irradiated individuals, showed a more remarkable increase of melanocytes than was evident in any of the normal oesophageal samples. There were no significant differences in incidence between males and females, or between age groups. In cases where the cancer invaded into deeper stroma, the melanocytes were mainly observed in the normal epithelium around the carcinomas. Epithelial and stromal elements of the melanotic mucosa commonly showed hyperplastic changes such as acanthosis or basal cell hyperplasia, and chronic oesophagitis. Melanocytes were observed most commonly in the lower part of the oesophagus, the site where malignant melanoma of the oesophagus, most often originates. These results strongly suggest that the melanocyte increase observed in areas of hyperplastic epithelium and chronic oesophagitis may play an important role as a precursor lesion for malignant melanoma in the oesophagus.

Asian People↗

PubMed1990

High yields of granulosa cell tumors/luteomas in F344 rat ovaries after transplacental administration of N-nitrosobis(2-oxopropyl)amine.

Ovarian tumors were induced at very high incidence in the offspring of F344 rats receiving 3 subcutaneous injections of 10 mg/kg of N-nitrosobis(2-oxopropyl)amine on the 14th, 18th and 20 days of gestation. Histologically, all ovarian tumors were of the granulosa cell tumor and/or luteoma type. Many of them consisted of large, polygonal cells with abundant eosinophilic or vacuolated cytoplasm, arranged in sheets or in a pseudo-palisaded pattern separated by thin fibrovascular stroma, and they exhibited typical luteoma morphological character. The high yields, and the similarities in morphology as well as putative hormonal influence suggest that this experimental system may serve as a good animal model for granulosa cell tumor and/or luteoma development in women.

Animals↗

PubMed1990

Tumor promoting effect of goitrogens on the rat thyroid.

To evaluate the mechanism of the promoting effect of goitrogens on thyroid tumorigenesis, well-known goitrogens having different pharmacologic action, i.e., thiourea, phenobarbital sodium (PB), potassium thiocyanate (KSCN), and 3,4,5,6-tetrachloro-2',4',5',7'-tetraiodo-fluorescein sodium salt (Rose Bengal B, FD&C Red No. 105) (FR105) were administered to the DHPN-initiated and non-initiated F344 male rats in the drinking water for 25 weeks. Remington's iodine deficient diet (I-def) was fed as a positive control. These goitrogens showed significant tumor promoting effect or promoting tendency on the rat thyroids. According to the changes in thyroid morphology and thyroid-related hormone titers observed in the present study, we proposed to classify goitrogens at least into 2 groups, i.e., iodine deficiency-type promoters and the iodine excess-type promoters. The former contains goitrogens inducing TSH-stimulated diffuse goiter composed of uniform follicles with activated tall follicular epithelial cells, such as thiourea, KSCN and PB, and the latter contains goitrogens inducing colloid goiter composed of a mixture of colloid-rich follicles with flat follicular cells and normal-looking follicles with cuboidal follicular cells, such as FR105. This classification may be useful for the risk assessment of goitrogens.

Animals↗

PubMed1988

Carcinogenicity and organ specificity of N-trimethylsilylmethyl-N-nitrosourea (TMS-MNU), N-neopentyl-N-nitrosourea (neoPNU), and N-methyl-N-nitrosourea (MNU) in rats.

The carcinogenicity and organ specificity of TMS-MNU and neoPNU, a carbon-analogue of TMS-MNU, in rats were investigated and compared with those of MNU. Compounds were dissolved in olive oil and rats in the experimental groups received 20 weekly intragastric intubations of 10 mg/kg of MNU or equimolar amounts of TMS-MNU or neoPNU in the same manner. The experiment was terminated when the survivors were sacrificed at the 52nd week after the final administration. In the TMS-MNU and MNU groups, tumors of the forestomach were induced and the incidence was 100% in the groups of both sexes. In addition, tumors of the glandular stomach, nervous system, kidney, and lung were also observed in these groups. Neurogenic tumors were found more frequently in the MNU group than in the TMS-MNU group. The incidence of lung tumors, however, was higher in the TMS-MNU group than in the MNU group. On the other hand, in the control and neoPNU groups, no tumor was found in these organs except the lung, and all tumors observed in these two groups were histologically similar to spontaneous ones in this strain of rats. These results indicate that the carcinogenicity of N-alkyl-N-nitrosoureas is dependent on the chemical structure of their alkyl chain. The result of the present study coincides with the previous result that the species of TMS-MNU in the alkylating step is the same as that of MNU, but different from neoPNU. The difference in the organ specificity between TMS-MNU and MNU demonstrates that the organ specificity is dominantly dependent on the distribution of the chemicals, since TMS-MNU may possibly be distributed differently from MNU because of its different partition property.

Animals↗

PubMed1987

Malignant endothelioma of the aorta.

An untreated case of a malignant endothelial tumour of the thoracic aorta of a 67 year-old male is reported. A tumour, 7 x 6 x 1.5 cm in size occupied the lumen of the descending thoracic aorta and two daughter lesions, 0.5 cm in diameter, were located in the abdominal aorta and the left common iliac artery. Histologically, they were composed of a surface cellular lining and a underlying necrotic mass; the former was six to ten layers of bizarre epithelioid cells thick and the latter contained much nuclear debris. Innumerable tumour emboli of epithelioid tumour cells and producing ischaemic lesions were found in various organs and tissues. Ultrastructurally, tumour cells were arranged in acinar pattern with narrow lumena and immature basement membrane. There were ultrastructural appearances interpreted as Weibel-Palade bodies and immunohistochemically factor VIII related antigen and vimentin was seen in the tumour cells.

Aged↗

PubMed1987

Lack of carcinogenicity of tartrazine (FD & C Yellow No. 5) in the F344 rat.

The carcinogenicity of tartrazine (C. I. Food Yellow No. 4, FD & C Yellow No. 5), a food, drug and cosmetics colouring, was examined in F344 rats. Tartrazine was dissolved in distilled water at levels of 0, 1 or 2%, and groups of about 50 male and 50 female rats were given one of these solutions ad lib. as their drinking-water for up to 2 yr. No toxic lesions specifically caused by tartrazine were detected in any treated group of either sex. Many tumours developed in all groups including the control group, and the organ distribution of these tumours and their histological characteristics were similar to those of the spontaneous tumours that are known to occur in this strain of rats. Except for mesothelioma in males and endometrial stromal polyp in females, there were no significant increases in the incidences of any tumours over those in the corresponding control group. In males, mesotheliomas were found only in the group given 1% tartrazine and the incidence of this lesion was statistically significant (Fisher's exact test) in comparison with the other two groups (P less than 0.02). The incidence of endometrial stromal polyp was also significantly higher among females given the 1% dose than in the controls (P less than 0.05). However, no positive trend was noted in the occurrence of these two tumours using an age-adjusted statistical analysis. Mesothelioma and endometrial stromal polyp are frequently observed spontaneous tumours in this strain of rats, and their incidences in our historical controls are 4.1 and 21.9%, respectively. However in the present study mesothelioma occurred in none of the male control rats and the incidence of endometrial stromal polyp was only 10.6% in the female control group. Moreover, there was no significant difference between the control and treated groups in hyperplastic or pre-neoplastic changes in the mesothelium or endometrium. From these findings, we concluded that the significant increases in the incidences of mesothelioma and endometrial stromal polyp that occurred in the groups given 1% tartrazine were not attributable to tartrazine administration. Thus, it is concluded that tartrazine was not carcinogenic in F344 rats when administered continuously at doses of up to 2% in the drinking-water for up to 2 yr.

Animals↗

PubMed1987

Induction of melanogenesis in Schwann cell and perineural epithelium by 9,10-dimethyl-1,2-benzanthracene (DMBA) and 12-o-tetradecanoylphorbol-13-acetate (TPA) in BDF1 mice.

Six-week-old female BDF1 mice were treated with a single topical application of DMBA followed by repeated application of TPA on the clipped dorsal skin. Several weeks after DMBA application, the intradermal melanocytes of perifollicular melanocytic network began to proliferate to form melanocytic tumors in all treated mice skin. Besides these changes, single membrane-bound melanosomes and premelanosomes were found in the cytoplasm of perineural epithelia and Schwann cells with mesaxons of the nerve bundles involved, and the melanogenic activity of the Schwann cell and the perineural epithelium of the dermal peripheral nerve bundle was discussed in terms of a common feature of neuro-ectodermal cells.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1987

Analysis of morphological factors of hepatocellular carcinoma in 98 autopsy cases with respect to pulmonary metastasis.

The morphological features of ninety-eight autopsy cases of hepatocellular carcinoma (HCC) were analyzed in relation to pulmonary metastasis. Extrahepatic hematogenous metastasis was observed in 64% and lung was most frequently involved (62%). A close relationship was observed between intrahepatic vascular invasion and extrahepatic hematogenous metastasis to lungs. Portal vein-invasion was found in 80% of cases and significant correlations were recognized between the rates of portal vein-invasion and hepatic vein-invasion, and between the rates of portal vein-invasion and pulmonary metastasis. There was a close correlation among the macroscopic growth-pattern, incidence of vascular invasion, and pulmonary metastasis, and their degrees. Namely, the expansive type HCC showed significantly lower rates of vascular invasion and pulmonary metastasis than the infiltrative or mixed type HCC. These rates were particularly low in the expansive type, single nodular subtype HCC with size of a primary tumor less than 10 cm. Significantly low rates of pulmonary metastasis and portal vein-invasion were also noted in well-differentiated carcinoma (Grade I or II). The existence of cirrhosis or fibrosis of liver in cases with HCC was not definitely related to the occurrence of pulmonary metastasis. It was originally clarified that invasion to the portal vein and the size of HCC played a main role in pulmonary metastasis.

Adult↗

PubMed1987

Glandular changes associated with the spontaneous interstitial cell tumor of the rat testes.

Testes of untreated F344 and Wistar rats in the control groups of carcinogenicity studies were histologically examined, and the histopathological characteristics and histogenesis of glandular changes in these testes were studied. In 266 testes of 2-year-old F344 rats, 263 had interstitial cell tumors (ICTs) (98.9%) and 39 had glandular changes (14.7%). These glandular changes were also found in 1 out of 38 1-year-old F344 rat testes (2.6%), and 3 in 154 2-year-old Wistar rat testes (1.9%). The changes were observed exclusively in the interstitial cell tumors (ICTs). These glandular changes showed variation in size, shape and number. They were composed of tubules or cysts lined by a layer of cuboidal or columnar epithelial cells, which had terminal bars, occasionally PAS- and alcian blue-positive brush borders, and rarely, alcian blue-positive cytoplasmic vacuoles. Serial sections revealed that the changes were not connected with the rete testes, but with the degenerative seminiferous tubules involved in the ICTs lined by a layer of flat endothelial-like cells. The findings suggest that the lesions constitute metaplastic changes of the Sertoli cells.

Animals↗

PubMed1987

Experimental induction of ovarian Sertoli cell tumors in rats by N-nitrosoureas.

Spontaneous ovarian tumors are very rare in ACI, Wistar, F344 and Donryu rats; the few neoplasms found are of the granulosa/theca cell type. Ovarian tumors were also rare in these strains of rats when given high doses of N-alkyl-N-nitrosoureas continuously in the drinking water for their life-span; however, relatively high incidences of Sertoli cell tumors or Sertoli cell tumors mixed with granulosa cell tumors were induced in Donryu rats after administration of either a 400 ppm N-ethyl-N-nitrosourea solution in the drinking water for 4 weeks or as a single dose of 200 mg N-propyl-N-nitrosourea per kg body weight by stomach tube. Typical Sertoli cell tumors consisted of solid areas showing tubular formation. The tubules were lined by tall, columnar cells, with abundant, faintly eosinophilic, often vacuolated cytoplasm, and basally oriented, round nuclei, resembling seminiferous tubules in the testes. In some cases, Sertoli cell tumor elements were found mixed with areas of granulosa cells. The induction of ovarian Sertoli cell tumors in Donryu rats by low doses of nitrosoureas may provide a useful model for these tumors in man.

Animals↗

PubMed1987

Long-term studies on carcinogenicity and promoting effect of phenylbutazone in DONRYU rats.

The carcinogenicity and promoting effect of phenylbutazone were investigated in inbred DONRYU rats. In the carcinogenicity study, both sexes were administered the chemical at dietary levels of 0 (control), 0.125, or 0.25% for 2 years. Toxic lesions were associated with phenylbutazone treatment in the kidney and digestive tract, appearing to have an adverse effect on life expectancy. Various tumors were detected in all groups including the controls. With the exception of pheochromocytoma in the female high-dose group, no statistically significant increase in yield of any tumors, including leukemia, was apparent in the treated groups of either sex when the data were analyzed by Fisher's exact probability and/or chi-square tests. Application of an age-adjusted statistical analysis revealed a slight positive effect regarding the occurrence of pheochromocytomas, neoplastic liver nodules, and leukemias in females. However, these tumors are commonly observed to develop spontaneously in this rat strain, and no such effect was apparent in the male groups. In addition, no differences in incidences of relevant preneoplastic lesions were evident between control and treated groups. Thus phenylbutazone showed no carcinogenic activity in DONRYU rats when given continuously in the diet for 2 years. For the investigation of promoting effect, phenylbutazone was given as a dietary supplement for 2 years subsequent to initiation with N-ethyl-N-nitrosourea or N-propyl-N-nitrosourea. No enhancement of nitrosourea-induced leukemogenesis was apparent, although a slight promoting effect was demonstrated for renal and thyroid tumorigenesis.

Adrenal Gland Neoplasms↗

PubMed1986

Gangliosides as markers of cortisone-sensitive and cortisone-resistant rabbit thymocytes: characterization of thymus-specific gangliosides and preferential changes of particular gangliosides in the thymus of cortisone-treated rabbits.

Neutral glycosphingolipids and gangliosides in rabbit thymus, spleen, bone marrow, and erythrocyte ghosts were analyzed by conventional chemical and enzymatic procedures and negative ion fast atom bombardment mass spectrometry (FABMS). Thymus gangliosides showed a characteristic composition. Major gangliosides comprising 75% of the total thymus gangliosides were sialosyl lacto-N-neo-tetraosyl- and sialosyl lacto-N-nor-hexaosylceramides containing NeuGc and palmitic acid. These major thymus gangliosides were not detected in spleen, bone marrow, or erythrocytes, whereas GD1a, which was not present in the thymus even in a trace amount, was present in spleen and bone marrow. In addition, the major gangliosides in rabbit thymus were preferentially reduced when an animal was given an intraperitoneal injection of cortisone acetate, as found on analysis 48 h later. The decrease was accompanied by a concomitant increase in NeuAc-containing GM3 with longer chain fatty acids.

Animals↗

PubMed1986

Induction of Sertoli cell tumors in the rat ovary by N-alkyl-N-nitrosoureas.

Relatively high incidences of Sertoli cell tumors of the ovary were induced in Donryu rats given a 400 ppm N-ethyl-N-nitrosourea solution as drinking water for 4 weeks or a single dose of 200 mg/kg N-propyl-N-nitrosourea by stomach tube. Typical Sertoli cell tumors were composed of solid areas showing tubular formation. Tubules were lined by tall, columnar cells having abundant, faintly eosinophilic, often vacuolated cytoplasm, and basally oriented round nuclei. In some cases, Sertoli cell tumors were found to be mixed with granulosa cell tumors.

Animals↗

PubMed1986

Lack of carcinogenicity of triethanolamine in F344 rats.

The carcinogenic potential of triethanolamine was examined in F344 rats. Triethanolamine was dissolved in distilled water at levels of 0 (control), 1, and 2%, and groups of 50 males and 50 females were given these doses ad libitum as drinking water for 2 yr. The dose levels in females were reduced by half from wk 69, because of associated nephrotoxicity. A variety of tumors developed in all groups, including the control group, and all tumors observed were histologically similar to spontaneous tumors in this strain of rats. No statistically significant increase of the incidence of any tumor was observed in the treated groups of both sexes by the chi-square test. In this study, however, there was an increase in nephrotoxicity, which appeared to have an adverse effect on the life expectancy of the treated animals, especially of females. Therefore, an age-adjusted statistical analysis on incidences of main tumors or tumor groups of both sexes was also done by methods recommended by Peto et al. (1980). The result showed that a positive trend (p less than 0.05) was noted in the occurrence of hepatic tumors (neoplastic nodule/hepatocellular carcinoma) in males and of uterine endometrial sarcomas and renal-cell adenomas in females. These tumors, however, have been observed spontaneously in this strain of rats, and their incidences in the control group of the present study were lower than those of our historical controls. These results may indicate that a positive trend in the occurrence of these tumors is not attributable to triethanolamine administration. Increased incidence of renal tumors in the female high-dose group may have been connected with renal damage. Histological examination of renal damage observed in the treated groups, especially in the female high-dose group, revealed acceleration of so-called chronic nephropathy. In addition, mineralization of the renal papilla, nodular hyperplasia of the pelvic mucosa, and pyelonephritis with or without papillary necrosis were also observed. Thus, it is concluded that under these experimental conditions triethanolamine is not carcinogenic in F344 rats but is toxic to the kidneys.

Animals↗

PubMed1986

Carcinogenicity of N-alkyl-N-(1-hydroperoxyalkyl) nitrosamines after intravenous injections in F344 rats.

As model compounds of alpha-hydroxy N-nitrosamines, four alpha-hydroperoxy N-nitrosamines were tested for their carcinogenic potential in F344 rats by i.v. injections. Correlation between chemical structure and carcinogenic potencies with respect to target organs was examined. Compounds used in this study were N-methyl-N-(hydroperoxymethyl)nitrosamine (MHPMN), N-ethyl-N-(1-hydroperoxyethyl)nitrosamine (EHPEN), N-propyl-N-(1-hydroperoxypropyl)nitrosamine (PHPPN) and N-butyl-N-(1-hydroperoxybutyl)nitrosamine (BHPBN). All chemicals were dissolved in distilled water and rats received 10 X 1 weekly i.v. injections of these chemicals (10 X 1 weekly injection of 5 mg/kg of MHPMN or equimolar amounts of other chemicals). Lung tumors were detected in all groups of both sexes and the incidences were 100% in each group. Thyroid tumors were also observed with relatively high incidences in treated groups except BHPBN. In the control group, tumors were observed mainly in the testis or uterus, and only two lung tumors and one thyroid tumor were observed in females. Histologically, all lung tumors in the MHPMN group were adenocarcinomas, squamous cell carcinomas or a mixture of both types. In the EHPEN, PHPPN and BHPBN groups, especially in females, incidences of carcinomas decreased as the length of the alkyl chain of the compounds, and most of lung tumors in females of the PHPPN and BHPBN groups were adenomas. Many of the thyroid tumors observed in the treated groups were follicular adenomas/carcinomas, whereas C-cell adenomas were the most common type of spontaneous thyroid tumors in this strain of rats. These target organs were similar to those of alpha-acetoxy N-nitrosamines reported previously. The results indicate that the carcinogenic activities of these chemicals depend on the length of the alkyl chain and that organ specificity of these chemicals may differ from those of their mother compounds.

Animals↗