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Biomedical subjects

N Yoshimi

Publications and source records attributed to N Yoshimi.

At least 91 records · Page 5Linked to original sources
PubMed1995

The mRNA overexpression of inflammatory enzymes, phospholipase A2 and cyclooxygenase, in the large bowel mucosa and neoplasms of F344 rats treated with naturally occurring carcinogen, 1-hydroxyanthraquinone.

Inflammation has been considered to be related to carcinogenesis. Previously, we demonstrated that 1-hydroxyanthraquinone (1-HA), a naturally occurring carcinogen, induced severe inflammation such as ulcerative colitis in colonic mucosa. We also showed that indomethacin inhibited the tumorigenicity of 1-HA. In this study, we examined the expressions of major enzymes in arachidonic acid cascade related to inflammation in the colon mucosa of rats treated with 1-HA. After the treatment of 1% 1-HA diet, colon lesions were observed and RNA was extracted from mucosa and neoplasms. The mRNA expressions of group II phospholipase A2, cyclooxygenase-2 and 5-lipoxygenase, were examined by using a reverse transcriptase polymerase chain reaction. The expressions of phospholipase A2 and cyclooxygenase were significantly increased in non-neoplastic mucosa in rats treated with 1-HA compared with those in control rats. The expressions in the neoplasms induced by 1-HA were also increased. Phospholipase A2, especially, was much higher in the neoplasms than in non-neoplastic mucosa. However, the expression of 5-lipoxygenase showed no change in the non-neoplastic mucosa and neoplasms of rats treated with 1-HA, compared with that in control rats. These findings suggest that the inflammation induced by 1-HA may be related to the metabolites through a cyclooxygenase pathway, which indicates a prostaglandin synthesis, but not through a lipoxygenase pathway, which indicates a leukotriene synthesis in arachidonic acid cascade.

Animals↗
PubMed1995

No involvement of Ki-ras or p53 gene mutations in colitis-associated rat colon tumors induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate.

1-Hydroxyanthraquinone (1-HA), which is present in some herbs, and methylazoxymethanol (MAM) acetate, a metabolite of azoxymethane, show synergistic carcinogenicity in rat colon, and 1-HA induces ulcerative changes with simultaneous severe inflammation of the entire colon. In this study, mutations in Ki-ras (exons 1 and 2) and p53 (exons 4-7) were studied by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Of 18 adenomas and 38 adenocarcinomas induced in male F344 rats (52 tumors induced by 1-HA plus MAM acetate, three by 1-HA alone, and one by MAM acetate alone), no mutations in Ki-ras or p53 were detected under two conditions of PCR-SSCP analysis. Because human colon carcinomas from patients with ulcerative colitis have a very low incidence of Ki-ras mutation, this experimental system would be a good animal model of human colon carcinomas with ulcerative colitis and of human colon carcinomas without Ki-ras or p53 mutations.

Animals↗
PubMed1995

Infrequent Ha-ras mutations and absence of Ki-ras, N-ras, and p53 mutations in 4-nitroquinoline 1-oxide-induced rat oral lesions.

The alkylating agent 4-nitroquinoline 1-oxide (4-NQO) is a powerful carcinogen and induces squamous cell hyperplasia, squamous cell dysplasia, papilloma, and squamous cell carcinoma (SCC) in rat oral epithelia. Oral cancers induced by a single application of 4-NQO develop through a multistage process in a way similar to the development of this cancer in humans. In this study, mutations in exons 1 and 2 of Ki-ras, N-ras, and Ha-ras and exons 4-7 of p53 were examined by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis, followed by PCR-direct sequencing for the confirmation of mutations. Samples for the mutation analysis were obtained from dysplasias, papillomas, and SCCs on the tongue epithelia induced in F344 rats by adding 4-NQO (20 ppm) to their drinking water for 8 wk. The Ha-ras mutations (61A-->T transversions in the second position) were found in five of 29 (17%) samples (one dysplasia and four SCCs). However, no mutations were detected in either Ki-ras, N-ras, or p53 under two different conditions of PCR-SSCP analysis. We suggest that some neoplasms in oral carcinogenesis induced by 4-NQO may involve Ha-ras mutations but not mutations in Ki-ras, N-ras, or p53. The 4-NQO-induced rat oral carcinogenesis model may provide a system for evaluation of the mechanisms of multistage oral carcinogenesis associated with Ha-ras mutation without Ki-ras, N-ras, or p53 mutation.

4-Nitroquinoline-1-oxide↗
PubMed1995

Hypothermic prevention of nuclear DNA fragmentation in gerbil hippocampus following transient forebrain ischemia.

The protective effect of hypothermia on DNA fragmentation following transient forebrain ischemia in mongolian gerbils was investigated. The DNA fragmentation demonstrated in situ in gerbil hippocampal CA1 was compared between intra- and post-ischemic hypothermia. Intra-ischemic hypothermia prevented the DNA fragmentation in hippocampal CA1 completely, while severe DNA damage was observed in post-ischemic hypothermia group. the degree of DNA fragmentation of hippocampal CA1 in the post-ischemic hypothermia group was equal to that in the ischemic control group. The results suggest that hypothermia during a transient forebrain ischemia exerts a protective effect on the post-ischemic hippocampal damage by preventing the DNA fragmentation in CA1 neurons.

Animals↗
PubMed1994

Reduced expression of phospholipase C-delta, a signal-transducing enzyme, in rat colon neoplasms induced by methylazoxymethanol acetate.

Phospholipase C (PLC), which hydrolyzes phosphoinositides, has been implicated as a key enzyme in signal transduction. We examined the expression of an isozyme of PLC, PLC-delta, in rat colon neoplasms induced by methylazoxymethanol (MAM) acetate. Large-bowel neoplasms were observed in five of 10 rats given MAM acetate (25 mg/kg body weight, by interperitoneal injection at 6 and 7 wk of age) 40 wk after treatment. Expression of PLC-delta in the neoplasms was not detected by northern blot analysis, and a low level of expression was detected by immunoblot analysis, although PLC-delta expression was apparent in the non-neoplastic colon mucosae of MAM acetate-treated rats as well as in the colon mucosae of control rats. Furthermore, analysis by reverse transcriptase-polymerase chain reaction revealed that the ratio of the expression of PLC-delta to that of beta-actin in the neoplasms was significantly lower than the ratios in the non-neoplastic colon mucosae of carcinogen-treated and control rats (P < 0.01). However, the ornithine decarboxylase (ODC) activity in the neoplasms was significantly greater than that of the non-neoplastic and control mucosae (P < 0.001). The differences in the levels of PLC-delta expression in neoplastic and non-neoplastic tissues and the inverse correlation of PLC-delta expression with ODC activity may suggest that PLC-delta has little effect on the PLC-mediated mitogenic signaling system, at least in MAM acetate-induced colon neoplasms in rats.

Animals↗
PubMed1994

Alterations of nuclear pores in preneoplastic and neoplastic rat liver lesions induced by 2-acetylaminofluorene.

The nuclear pore density and area were measured on freeze-fractured nuclei of ACI/N rat liver altered foci, adenomas and carcinomas induced by 2-acetylaminofluorene, and compared with those of normal hepatocytes. The pore density of nuclei from these preneoplastic and neoplastic lesions was significantly higher than that of hepatocytes, but there was no difference between lesions. The area of nuclear pores of the focus cells did not differ from normal hepatocytes, whereas the areas of pores of adenoma and carcinoma cells were increased. Moreover, the nuclear pore area of carcinomas was significantly greater than that of adenomas. These results suggest that some changes may occur in nuclear pores in the progress of tumorigenesis.

2-Acetylaminofluorene↗
PubMed1994

The inhibitory effect of magnesium hydroxide on the bile acid-induced cell proliferation of colon epithelium in rats with comparison to the action of calcium lactate.

The modulating effects of magnesium hydroxide and calcium lactate on the cholic acid-induced hyperproliferation of cells in rat colon epithelium were investigated. Rats were divided into six groups (10 rats/group) and fed the following diets for 8 weeks: 0.25% cholic acid alone (group 1), cholic acid plus 0.2% magnesium hydroxide (group 2), cholic acid plus 1.18% calcium in the form of calcium lactate (group 3), calcium lactate alone (group 4), magnesium hydroxide alone (group 5) and the basal diet alone (group 6). At the end of the experiment, all rats were killed for the immunocytochemical examination of 5-bromo-2'-deoxyuridine (BrdU) incorporation in the cell nuclei of colonic epithelium. Magnesium hydroxide reduced the cholic acid-induced BrdU incorporation by 33% at the distal part and 40% at the proximal part. Calcium lactate also reduced the BrdU incorporation by 48% and 51% respectively. Exposure of magnesium hydroxide or calcium lactate alone had no influence on BrdU incorporation. The results suggest that magnesium hydroxide might exert anti-carcinogenic effects as does calcium by reducing increased cell proliferation of colonic epithelium induced by toxic effects of bile acids, which are regarded as colon tumor promoters or cocarcinogens.

Animals↗
PubMed1994

Expression of cytokines, TNF-alpha and IL-1 alpha, in MAM acetate and 1-hydroxyanthraquinone-induced colon carcinogenesis of rats.

The expression of cytokines, TNF-alpha and IL-1 alpha, was examined by means of a reverse transcription followed by PCR (RT-PCR) in rat colon carcinogenesis. Forty male F344 rats were used and divided into four groups. At the start of the experiment, 20 rats were treated with methylazoxymethanol (MAM) acetate (25 mg/kg body wt, one time, i.p.) and divided into two groups; group 1 was exposed to 1% 1-hydroxyanthraquinone (1-HAQ) and group 2 was fed a basal diet during the experiment (40 weeks). Other rats were also divided into two groups; group 3 was exposed to 1% 1-HAQ as group 1, and group 4 was used as control. Tumor incidence (100%) and multiplicity (5.00 +/- 2.05) in group 1 were significantly greater than those in group 2 (20% and 0.2 +/- 0.42) and group 3 (10% and 0.10 +/- 0.32) (P < 0.01 and P < 0.01 respectively). RT-PCR technique with RNA was applied to the tissues from colon neoplasms and mucosa in each group. Expression of TNF-alpha and IL-1 alpha in the colon neoplasms was much stronger than that in the colon mucosa of each group (P < 0.001 and P < 0.01 respectively). The expression of TNF-alpha was more remarkable in the colon mucosa of group 1 than that in corresponding tissue of groups 2 and 3 (P < 0.01). The expressions of TNF-alpha and IL-1 alpha were more increased in the colon mucosa of groups 1, 2 and 3 than that in group 4 as control (P < 0.01 and P < 0.05 respectively). The results indicate that TNF-alpha and IL-1 alpha may act as growth factors in rat colon carcinogenesis by MAM acetate and 1-HAQ. In addition, the synergistic effect of 1-HAQ with MAM acetate in colon carcinogenesis might be related to biological effects of the cytokines expressed in the inflammatory condition generated by 1-HAQ.

Adenocarcinoma↗
PubMed1994

Promoting and synergistic effects of chrysazin on 1,2-dimethylhydrazine-induced carcinogenesis in male ICR/CD-1 mice.

The modifying effects of chrysazin on 1,2-dimethylhydrazine (DMH)-induced colon and liver carcinogenesis were examined in male ICR/CD-1 mice. Starting at 6 weeks of age, mice were divided into four groups, two of which were treated with s.c. injections of DMH (20 mg/kg body wt) once a week for 12 weeks. A week after the final injection of DMH, one group was kept on the basal diet throughout the study (group I), and the other group was fed the diet containing chrysazin (mixed in basal diet at 0.2% concentration) alone for 42 weeks (group II). The other two groups were injected with normal saline and given the diet containing 0.2% chrysazin for 42 weeks (group III), or the basal diet during the experiment (group IV). The incidence and multiplicity of colon tumors of group II were significantly greater than those of group I (P < 0.05, P < 0.01). The incidence and multiplicity of the hepatocellular neoplasms of group II were larger than those of group I (P < 0.002, P < 0.02 respectively). In group III, colon tumors were not found, though a few liver neoplasms and severe inflammatory lesions of the colon were observed. The activity of ornithine decarboxylase of the colonic mucosa in mice exposed to chrysazin was stronger than that of animals without chrysazin. The results suggest that the promoting effect of chrysazin is probably related to an increase of cell proliferation in the target organ. A synergistic effect of DMH with chrysazin was also observed in liver tumorigenesis.

1,2-Dimethylhydrazine↗
PubMed1994

Inhibitory effect of topical application of polymerized ferulic acid, a synthetic lignin, on tumor promotion in mouse skin two-stage tumorigenesis.

A dehydrogenation polymer of ferulic acid (DHP-FA), a synthetic lignin, was evaluated for its ability to inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the 7,12-dimethylbenz[a]anthracene-treated skin of female ICR mice. Topical application of DHP-FA inhibits TPA-induced tumor promotion, whereas a monomeric ferulic acid does not show the inhibitory effect.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Inhibitory effects of magnesium hydroxide on c-myc expression and cell proliferation induced by methylazoxymethanol acetate in rat colon.

The effects of magnesium hydroxide were examined on methylazoxymethanol (MAM) acetate-induced c-myc expression and cell proliferation of colonic mucosal epithelium in rats. Rats were divided into four groups and treated as follows: MAM acetate alone (25 mg/kg i.p. injection, five times, once a week for 5 weeks), MAM acetate and feeding of 0.2% magnesium hydroxide in diet, magnesium hydroxide alone and non-treatment. At 4, 8 and 16 weeks after the start of experiment, 10 rats in each group were sacrificed. Magnesium hydroxide inhibited the MAM-induced expression of c-myc proto-oncogene, and also suppressed the increased bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) labelling indexes induced by MAM acetate in colon mucosa in initiation and post-initiation phase. These results suggest that the anti-carcinogenic effect of magnesium hydroxide on rat colon carcinogenesis induced by MAM acetate may be related to the inhibition of the carcinogen-induced expression of c-myc proto-oncogene and cell proliferation.

Animals↗
PubMed1993

Chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis by a simple phenolic acid protocatechuic acid in rats.

The modifying effect of dietary protocatechuic acid (PCA) given during the initiation phase or the postinitiation phase on liver carcinogenesis induced by diethylnitrosamine (DEN) was studied in male F344 rats. At 6 weeks of age, rats were divided into experimental and control groups and fed the diets containing 500 and 1000 ppm PCA or the basal diet. At 7 weeks of age, all animals except PCA alone and control groups were given DEN at 40 ppm in the drinking water for 5 weeks to induce liver cell neoplasms. Seven days after the DEN exposure, groups of animals fed the PCA diets and continued on these diets until the end of the study. All animals were necropsied during the 37 weeks after the start of the experiment in order to determine the incidences of preneoplastic liver cell foci and neoplasms. Hepatic ornithine decarboxylase activity was also measured in all animals at the termination of the study. Dietary PCA administered at both doses during the initiation phase significantly inhibited the incidence of altered hepatocellular foci resistant for iron accumulation or those positive for glutathione S-transferase placental form and the liver cell tumor incidence and multiplicity. Similarly, the numbers of liver cell foci and neoplasms and tumor multiplicity were significantly reduced in groups fed the PCA diets at the postinitiation stage of carcinogenesis. Hepatic ornithine decarboxylase activity was reduced in DEN-treated animals fed the PCA diets compared to those given DEN alone. Although the precise mechanisms of PCA-induced inhibition of hepatocarcinogenesis remain to be elucidate, it is likely that the inhibitory effects during the initiation and postinitiation phases may be due to alteration in hepatic ornithine decarboxylase activity under the present experimental condition.

Animals↗
PubMed1993

Expression of the placental form of glutathione S-transferase in pediatric gliomas.

Expression of the human placental form of glutathione S-transferase (GST-pi) in pediatric gliomas, consisting of three pilocytic astrocytomas (grade 1), two fibrillary astrocytomas (grade 2), three anaplastic astrocytomas (grade 3), and one glioblastoma multiforme (grade 4), were investigated by immunohistochemical methods. Western blot analysis for GST-pi using proteins extracted from formalin-fixed and paraffin-embedded glioma specimens was performed and compared with the results of immunohistochemistry. Both the immunohistochemical examination and the Western blot analysis of pediatric gliomas revealed that malignant gliomas such as anaplastic astrocytoma and glioblastoma had strong expression of GST-pi while benign gliomas showed weak GST-pi expression.

Adolescent↗
PubMed1993

Identification of placental form of glutathione S-transferase in ACNU-resistant murine glioma cell lines.

Expression of the placental form of glutathione S-transferase (GST-P) in 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloro-ethyl)-3-nitrosourea hydrochloride (ACNU)-sensitive 9L and C6 glioma cells, and ACNU-resistant 9L (9LR) and C6 (C6R) glioma cells was investigated by Northern blot analysis for GST-P mRNA and Western blot analysis for GST-P protein. The sensitivity of 9L, 9LR, C6 and C6R cell lines to ACNU was evaluated by microculture tetrazolium assay. Localization of GSTP-P protein in these cell lines was investigated by immunocytochemical method. Expression level of GST-P mRNA in 9LR cells was 3 times that of 9L cells and the level of GST-P protein in 9LR cells was 1.7 times that of 9L cells. On the contrary, the amount of GST-P mRNA of C6R cells was 1.3-fold larger than C6 cells and that of GST-P protein of C6R cells was 1.3-fold larger than C6 cells. Immunocytochemical investigation revealed that 9LR cells had stronger expression of GST-P in their cytoplasm than 9L cells. Expression of GST-P in both C6R and C6 cells was less than 9L and 9LR cells, and the amount was similar to each other. The present study suggests that GST-P may play an important role in detoxification of anti-cancer drugs in some glioma cells.

Animals↗
PubMed1993

Immunoblot analysis of the placental form of glutathione S-transferase in protein extracted from paraffin-embedded human glioma tissue.

Protein extracted from conventional formalin-fixed and paraffin-embedded tissue sections of human gliomas was examined for immunoblot analysis using antibody against the placental form of glutathione S-transferase (GST-pi). Four benign astrocytomas, five anaplastic astrocytomas and four glioblastomas were used in this study. The preliminary study demonstrated that immunoreactivity of GST-pi was well preserved in normal brain tissue and normal term placenta fixed in acetone, formalin or buffered formalin (pH 7.4). GST-pi in gliomas fixed in formalin also had a good immunoreactivity and showed clear bands on nitrocellulose membranes processed by the method of Western blotting using anti-GST-pi antibody. The results of immunoblot analysis for GST-pi indicate that the intensity of immunoreactivity of benign astrocytoma, anaplastic astrocytoma and glioblastoma increases with the advance of malignancy of these neoplasms. Western blot analysis for GST-pi can be performed using protein extracted from formalin-fixed and paraffin-embedded tissue sections, and the immunoreactive bands can be analyzed quantitatively by densitometric scanning.

Blotting, Western↗