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Biomedical subjects

N Yoshimi

Publications and source records attributed to N Yoshimi.

At least 127 records · Page 7Linked to original sources

The synergistic effect of 1-hydroxyanthraquinone on methylazoxymethanol acetate-induced carcinogenesis in rats.

The synergistic potential of 1-hydroxyanthraquinone (1-HA) on methylazoxymethanol (MAM) acetate-induced carcinogenesis was investigated in rats. A total of 154 inbred ACI/N rats (73 males and 81 females), six weeks old at the start of the experiment, were divided into four groups: group 1 was given i.p. injections of MAM acetate (25 mg/kg body wt), once per week for 2 weeks and then fed the diet containing 1% 1-HA for 42 weeks; group 2 received MAM acetate and was kept on the basal diet alone; group 3 was given 1-HA containing diet alone as for group 1; group 4 was treated as a control. At the termination of the experiment, the carcinogenic effect of MAM acetate and 1-HA in the large bowel or liver exceeded the sum of effects when given alone, indicating that the two chemicals act synergistically in the carcinogenesis of these organs.

Administration, Oral↗

Malignant mixed tumor (malignant ameloblastoma and fibrosarcoma) of the maxilla.

We present a rare case of carcinosarcoma (malignant ameloblastoma and fibrosarcoma) of the left maxilla that developed in a 63-year-old Japanese man. The tumor recurred repeatedly despite multiple surgical removals, radiotherapy, and chemotherapy and led to progressive cachexia; the patient died after 3.8 years of hospitalization. Histopathologic examination revealed that the recurrent tumor was carcinosarcoma, which had progressed from malignant ameloblastoma with fibroma. An autopsy confirmed the diagnosis of malignant mixed tumor with lung metastasis of malignant ameloblastoma and fibrosarcoma.

Ameloblastoma↗

Inhibitory effects of chlorogenic acid, reserpine, polyprenoic acid (E-5166), or coffee on hepatocarcinogenesis in rats and hamsters.

Four different experiments were performed in order to examine the modifying effects of chlorogenic acid (CA), reserpine, polyprenoic acid (E-5166), and coffee on chemical carcinogenesis in rats or hamsters. Experiment 1: The numbers of hyperplastic liver cell foci and the incidence of colon tumors in male and female Syrian golden hamsters given a single intravenous injection of methylazoxymethanol (MAM) acetate and then fed the diet containing 0.025% CA for 24 wk were significantly lower than those of hamsters given MAM acetate alone. Experiment 2: The incidence of altered hepatocellular foci in female ACI/N rats given N-2-fluorenylacetamide (FAA, 0.02% in diet) for 10 wk and reserpine (weekly subcutaneous injections, 1 microgram/g body weight) during or after (17 wk) FAA exposure was significantly lower than that of rats given FAA alone. Experiment 3: The number of hepatocellular foci in male ACI/N rats given 0.02% FAA diet for 13 wk and E-5166 by gavage (40 mg/kg body weight, 3 times/wk) for 16 wk after the end of FAA exposure was significantly smaller than that in rats given FAA diet alone. Experiment 4: Incidences of liver tumors and hepatocellular foci of rats given concurrent dietary administration of aminopyrine (0.01%) and sodium nitrite (0.1%) and coffee solution as a drinking water for 630 da were significantly lower than those of rats given aminopyrine and sodium nitrite. Thus, the tested compounds had inhibitory effects on chemical carcinogenesis in liver or colon.

Animals↗

Genotoxicity of heterocyclic amines in the hepatocyte/DNA repair assay using hepatocytes of rats or mice pretreated with 3-methylcholanthrene.

The genotoxicity of 4 heterocyclic amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) was examined in the hepatocyte primary culture (HPC)/DNA-repair assay using hepatocytes of rats and mice pretreated with 3-methylcholanthrene (MC), and the results were compared with those obtained in a previous assay with hepatocytes of normal rodents. All of these heterocyclic amines clearly elicited positive responses of DNA repair in the assay with hepatocytes of the rodents given MC, although in the regular HPC/DNA-repair test without MC pretreatment Tyr-P-2 and Glu-P-2 were negative in rat hepatocytes, and Try-P-2 was also negative in mouse hepatocytes. The level of unscheduled DNA synthesis induced by these positive compounds in the assay with hepatocytes of MC-treated rodents was much higher than that in the assay with hepatocytes of normal rodents. These results are basically in agreement with the reports that this class of compounds is highly activated metabolically by the cytochrome P-450 system from liver microsomes.

Amines↗

Carcinogenicity of naturally occurring 1-hydroxyanthraquinone in rats: induction of large bowel, liver and stomach neoplasms.

The carcinogenic potential of 1-hydroxyanthraquinone (HA), a naturally occurring compound, was examined. A total of 60 male ACI/N rats, 1.5 months old at the commencement were divided into two groups. Group 1 (30 rats) were fed the diet containing HA at a concentration of 1% throughout the experiment (480 days). Group 2 (30 rats) served as the control given a basal diet alone. Twenty-five of 29 effective animals in group 1 developed adenomas or adenocarcinomas in the cecum or upper portion of the colon, the mean number of large bowel tumors/tumor bearing rat being 2.3. In addition to these intestinal tumors, liver neoplasms (neoplastic nodules and hepatocellular carcinomas) were observed in 12 rats and benign stomach tumors were obtained in five animals; no rats of group 2 demonstrating development of any of these tumor types. The incidences of the large bowel, liver and stomach neoplasms in group 1 were all significant as compared with group 2 (P less than 2 x 10(-13), P less than 5 x 10(-5) and P less than 3 x 10(-2) respectively) clearly indicating that HA is carcinogenic in rats.

Animals↗

Fine-needle aspiration cytology of pheochromocytoma-ganglioneuroma of the organ of Zuckerkandl.

Fine-needle aspiration (FNA) cytologic and immunocytochemical findings of a rare combined pheochromocytoma-ganglioneuroma developing in a 48-yr-old Japanese man in the organ of Zuckerkandl are described. This is the first report of a combined pheochromocytoma-ganglioneuroma of the organ of Zuckerkandl. FNA cytology showed typical cytologic findings of these two components similar to those described individually in fine-needle aspirates of these neoplasms. The neoplastic cells showed positive reactions for vasoactive intestinal polypeptide, neuron-specific enolase, and S-100.

Biopsy, Needle↗

Simultaneous occurrence of medullary and follicular carcinoma in the same thyroid lobe.

A rare case of the simultaneous development of medullary and follicular carcinoma of the thyroid gland in a 51-year-old Japanese woman is examined. A preoperative diagnosis was made by needle aspiration cytology. Neoplastic cells of the medullary carcinoma were positive for calcitonin and carcinoembryonic antigen, whereas the tumor cells of the follicular carcinoma were negative for these substances. This case presents evidence that, in rare cases, two malignant epithelial neoplasms of different origins can occur in the same lobe of the thyroid.

Adenocarcinoma↗

Inhibitory effect of magnesium hydroxide on methylazoxymethanol acetate-induced large bowel carcinogenesis in male F344 rats.

The effect of dietary magnesium hydroxide on colon carcinogenesis induced by methylazoxymethanol (MAM) acetate was examined in male F344 rats. MAM acetate was administered by i.p. injection to rats at 25 mg/kg body wt once per week for 3 weeks. Starting 2 weeks after the final MAM acetate exposure, the diet containing 500 or 1000 p.p.m. magnesium hydroxide was fed for 227 days. In the groups receiving magnesium hydroxide and MAM acetate, the incidence of colon neoplasms was decreased when compared with that in the group given MAM acetate alone. The inhibitory effect of dietary magnesium hydroxide on MAM acetate-induced colon carcinogenesis was greater at the lower dose than that at the higher dose of magnesium hydroxide in the diet. Neoplasms in other organs were rare and were not affected by the dietary magnesium hydroxide.

Animals↗

Induction of altered hepatocellular foci of hamster for a possible short-term assay for carcinogens.

Altered hepatocellular foci of hamster were applied for in vivo short-term (8 weeks) assay for detecting carcinogens using dietary exposure of N-2-fluorenylacetamide (FAA) and oral administration of carbon tetrachloride (CCl4). Although no hepatocellular foci were induced by the treatment with either of two agents (FAA and CCl4) or with their combination, many of the lesions appeared in the hamsters with prior administration of carcinogens, i.e., dimethylnitrosamine, diethylnitrosamine and methylazoxymethanol acetate, all of which have been reported to be carcinogenic in hamsters. A small number of these lesions was also present with the pretreatment of other types of carcinogens, i.e., N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine and azaserine. No such foci were available by N-butyl-N-(4-hydroxybutyl)nitrosamine and 3,3'-dichloro-4,4'-diaminodiphenylmethane, both of which are not known to be clearly carcinogenic in hamsters. The results indicate that hepatocellular foci of hamsters are rapidly inducible under the present protocol and imply that this model could be useful as an assay for screening carcinogens of which hamster is susceptible.

2-Acetylaminofluorene↗

Reduced DNA repair response of carcinogen-induced hyperplastic cells in rat urinary bladder exposed to N-methyl-N'-nitro-N-nitrosoguanidine in organ culture.

DNA repair response to N-methyl-N'-nitro-N-nitrosoguadine (MNNG) was examined in an organ culture of hyperplastic urinary bladder epithelium, induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male F344 rats. Organ cultures of urinary bladders obtained from rats given a solution of 0.05% BBN for 4-12 weeks, were processed and exposed to MNNG (10(-3)M). The DNA repair response was estimated by autoradiographic analysis of unscheduled DNA synthesis (UDS). In general, hyperplastic cells of the urinary bladder induced by BBN showed lower UDS levels than those of non-hyperplastic cells. The reduction of DNA repair response to MNNG was more prominent in advanced hyperplastic cells with longer BBN treatment than in early appearing hyperplastic cells with shorter BBN treatment.

Animals↗

Species and sex differences in genotoxicity of heterocyclic amine pyrolysis and cooking products in the hepatocyte primary culture/DNA repair test using rat, mouse, and hamster hepatocytes.

Eleven mutagenic heterocyclic amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]-indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3]indole (Trp-P-2), 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-amino-9H-pyrido[2,3-b]indole (A alpha C), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo [4,5-f]quinoline (MeIQX), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-diMeIQX), and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-diMeIQX), were studied for genotoxicity in the hepatocyte/DNA repair test employing hepatocytes of male rats, male and female mice, and male hamsters. In these four assay systems, all compounds elicited DNA repair in at least three systems, except Trp-P-2, which was uniformly inactive. However, there were several significant differences in the responses of different systems. Rat and hamster hepatocytes responded to nine of the ten genotoxic compounds with the exception of Glu-P-2. Male and female mouse hepatocytes responded to Glu-P-2, whereas female, but not male, mouse hepatocytes responded to MeIQX and 4,8-diMeIQX. These results illustrate species and sex differences in response to these heterocyclic amines and suggest that a number of these compounds are carcinogenic in hamsters, as they have been in rats and mice.

Amines↗

Genotoxicity of epoxy resin hardeners in the hepatocyte primary culture/DNA repair test.

The genotoxicity of 9 chemicals used as epoxy resin hardeners was examined in the DNA repair test with rat hepatocytes. DNA repair synthesis was elicited by 7 chemicals, i.e., 4-aminodiphenyl ether, 4,4-diaminodiphenyl ether, 3,4,4'-triaminodiphenyl ether, 3,3'-dichloro-4,4'-diaminodiphenyl ether, 1,3-phenylenedi-4-aminophenyl ether, 4,4'-diaminodiphenyl methane and 4,4'-methylene-bis(2-chloroaniline). The positive results obtained with 4 epoxy resin hardeners of unknown carcinogenicity, i.e., 4-amino-diphenyl ether, 3,4,4'-triaminodiphenyl ether, 3,3'-dichloro-4,4'-diaminodiphenyl ether and 1,3-phenylene-di-4-aminophenyl ether suggest that they may be carcinogens. The genotoxicity of 1,4-phenylene-di-4-aminophenyl ether, of unknown carcinogenicity, and 4,4'-diaminodiphenyl sulfone, for which there is no sound proof of carcinogenicity, was not confirmed in the DNA repair test. The result with 4,4'-diaminodiphenyl sulfone was in agreement with its lack of mutagenicity in Salmonella typhimurium.

Animals↗

The genotoxicity of a variety of aniline derivatives in a DNA repair test with primary cultured rat hepatocytes.

The genotoxicity of a variety of aniline derivatives was examined by a DNA repair test with rat hepatocytes. Out of 37 aniline derivatives, 6 chemicals, i.e., 2,4,6-trimethylaniline (mesidine), 2,4-xylidine, 3,5-diaminobenzoic acid, 3,4-diaminochlorobenzene, 2-chloro-4-methylaniline and 4-chloro-N-methylaniline, elicited positive DNA repair responses. The results are in agreement with the bacterial mutagenicities with or without norharman of these compounds. Positive compounds of unknown carcinogenicity in the present assay, i.e., 3,5-diaminobenzoic acid, 2-chloro-4-methylaniline and 4-chloro-N-methylaniline are suspected of being potentially carcinogenic.

Aniline Compounds↗

An application of a quantitative analytical system for the grading of pulmonary fat embolisms.

The severity of pulmonary fat embolism in 5 autopsied cases has been measured using a quantitative image analytical system. With reference to the mean size of the fat emboli, the cases were divided into 2 groupings regardless of the number of the emboli. The mean sizes of the emboli in 3 cases of the first group were significantly larger (about 490-600 microns 2) than those found in the 2 cases of the other group (about 220 and 235 microns 2). An investigation into the localization of fat emboli revealed that more were lodging in the small arteries and arterioles in the first group than in the second. Our results have indicated that a reliable grading of pulmonary fat embolism can not be established without a quantitative image analysis of the size and localization of the fat emboli, and that this quantitative analytical method is useful in achieving this reliable grading.

Adolescent↗

Potential carcinogenicity of 5,6-dimethoxysterigmatocystin in rats.

The potential carcinogenic activity of 5,6-dimethoxysterigmatocystin (DMSC) was examined by oral administration in rats. In Experiment I, all of eight effective ACI/N rats given DMSC in the diet at a concentration of 50 p.p.m. developed neoplastic nodules of the liver. Five rats developed hepatocellular carcinomas and four rats had hemangioendothelial sarcomas of the liver. Two other rats developed osteosarcomas. In Experiment II, F344 rats were given DMSC by gavage once every 2 weeks at dose of 2 mg/0.15 ml dimethylformamide. Out of 24 effective animals 19 rats developed neoplastic nodules of the liver, and eight rats had hepatocellular carcinomas. Hemangioendothelial sarcoma of the liver was seen in one rat. Two rats developed osteosarcomas in the upper legs. Proliferative fibrous lesions which were considered to be a preneoplastic change of the bone tumors were seen in the thighbones of four rats. Results obtained from these two experiments indicate that DMSC is hepatocarcinogenic, as is sterigmatocystin, and that the compound is probably weakly carcinogenic for the bone.

Administration, Oral↗

Genotoxicity of a variety of hydrazine derivatives in the hepatocyte primary culture/DNA repair test using rat and mouse hepatocytes.

The genotoxicity of a variety of hydrazine derivatives was examined in the DNA-repair test on rat or mouse hepatocytes. Out of 32 hydrazine derivatives, 6 chemicals, i.e., N'-acetyl-4-(hydroxymethyl)phenylhydrazine, 1,2-dimethylhydrazine.2HCl, 1-hydrazinophthalazine.HCl, methylhydrazine.sulfate, p,p'-oxybisbenzene disulfonylhydrazide and phenylhydrazine.HCl, elicited positive DNA repair responses in the test on rat hepatocytes. In the test on mouse hepatocytes, 4 more hydrazine derivatives, i.e., 1,1-dimethylhydrazine, hydrazine hydrate, hydrazine sulfate and 2-methyl-4-chlorophenoxyacetic acid hydrazide.HCl also generated positive responses, in addition to the 6 positive compounds in the rat assay. These results suggest that mouse hepatocytes are more susceptible to the genotoxicity of hydrazine derivatives, and that the species differences in genotoxicity appear to be in agreement with the in vivo carcinogenicity of these agents.

Animals↗

Additional survey on genotoxicity of natural anthraquinones in the hepatocyte primary culture/DNA repair assay.

Genotoxicity of fungal anthraquinones of islandicin, iridoskyrin and (-) rubroskyrin, and a colorant of insect origin, cochineal and its component, carminic acid, an anthraquinone, was examined in the hepatocyte primary culture/DNA repair test. The results were compared with that of versicolorin A, an anthraquinone with bisfuran ring, which had been proved to be genotoxic on this assay. All of these anthraquinones, differently from versicolorin A did not show clear response of DNA repair. The results suggest that these agents are not genotoxic carcinogens.

2-Acetylaminofluorene↗

Immunohistochemical localization of human lung adenocarcinoma-associated antigen with a monoclonal antibody.

The monoclonal antibody, 5C7, reacted immunohistochemically with 62 out of bronchial cells of normal lung tissue, adjacent to neoplastic lesions, were negative for lung adenocarcinoma-associated antigen. Reactions with the antibody were observed in half the cases of squamous cell lung cancer, but were only sporadic. The antibody appears to react with an antigen which is either restricted to malignant cells or is at least greatly amplified in expression by malignant cells compared to normal human tissues. The major value of this monoclonal antibody at present is in classifying lung cancers as either adenocarcinoma or non-adenocarcinoma.

Adenocarcinoma↗