Bladder cancer producing granulocyte colony-stimulating factor.
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Carcinoma, Transitional Cell↗
Biomedical subjects
N Ito
Publications and source records attributed to N Ito.
Effects of bile acids on development of pepsinogen-altered pyloric glands in rats.
The effects of dietary bile acids on the development of pepsinogenaltered pyloric glands (PAPG) were examined. Male WKY/NCrj rats were given a single dose of 160 mg/kg body wt. of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by gastric intubation and fed basal diet containing 0.3% sodium taurocholate (Na-TC), 0.3% sodium cholate (Na-C), 0.3% sodium glycocholate (Na-GC), 0.3% sodium tauroglycocholate, 0.3% sodium deoxycholate, 0.1% chenodeoxycholic acid or 0.5% lithocholic acid for 14 weeks. All rats also received 1 ml of saturated NaCl solution 4 times by i.g. intubation. At the end of week 16, the animals were killed, and the number of PAPG per cm of mucosal length was determined immunohistochemically. Na-TC, Na-C and Na-GC significantly increased the number of PAPG over the control value, suggesting that they may have activity to promote gastric carcinogenesis.
Animals↗
Inhibition of rat hepatic glutathione S-transferase placental form positive foci development by concomitant administration of antioxidants to carcinogen-treated rats.
Inhibition potential of concomitant butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), catechol or sodium ascorbate (Na-AsA) administration on development of diethylnitrosamine (DEN) initiated glutathione S-transferase placental form (GST-P) positive foci in rat liver under the influence of 2-acetylaminofluorene (2-AAF) or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) plus partial hepatectomy (PH) was investigated. Whereas BHA, BHT and catechol exerted marked inhibitory effects, Na-AsA lacked any modifying potential. The compounds that demonstrated inhibition also induced GST-P in the hepatic periportal areas, suggesting that development of GST-P positive foci is negatively influenced by extra-focal increase in this enzyme form observed with BHA, BHT or catechol.
2-Acetylaminofluorene↗
Effects of naturally occurring antioxidants on combined 1,2-dimethylhydrazine- and 1-methyl-1-nitrosourea-initiated carcinogenesis in F344 male rats.
The effects of treatment with naturally occurring antioxidants, selenium, beta-carotene, ferulic acid, esculin and eugenol during the promotional phase of tumor development were investigated in male F344 rats pre-treated with 1,2-dimethylhydrazine (DMH) and 1-methyl-1-nitrosourea (MNU). Animals were given 3 subcutaneous injections of DMH at a dose of 40 mg/kg body wt. within 1 week and then were injected with MNU i.p. at a dose of 20 mg/kg body wt. 2 times per week, for 2 weeks. Thereafter, the rats were maintained on diet containing either 0.2% beta-carotene, 2 ppm selenium, 1% ferulic acid, 1% esculin or 0.8% eugenol. At week 52, surviving rats were killed and complete histological examinations were performed. Administration of eugenol enhanced the development of both hyperplasia and papillomas in the forestomach. Although treatment with beta-carotene tended to decrease the incidence and number of large intestinal carcinomas, beta-carotene, selenium, esculin and eugenol all decreased the incidence of kidney nephroblastomas, the differences were not statistically significant. The results thus showed that eugenol exerts promoting activity for forestomach carcinogenesis while the other antioxidants might have weak organ-specific inhibitory effects under these experimental conditions.
1,2-Dimethylhydrazine↗
Slalom chromatography: size-dependent separation of DNA molecules by a hydrodynamic phenomenon.
Slalom chromatography, a size-dependent DNA fractionation method based on a new principle [Hirabayashi, J., & Kasai, K. (1989) Anal. Biochem. 178, 336-341], was systematically studied in detail. In this method, larger DNA fragments are eluted much later than smaller ones from columns packed with spherical microbeads. Elution of a series of DNA fragments was systematically examined by using columns packed with polymer-based packings of different diameter and different pore size for high-performance gel permeation chromatography. Packings of smaller diameter proved to be superior for resolving the smaller size range of DNA, while the reverse was the case for larger DNAs. Application of a faster flow rate led to larger retardation of every DNA fragment, while at the lowest flow rate applied (0.067 cm/min), all the fragments were eluted almost at the void volume. When the column temperature was lowered, retardation of DNA became larger. On the other hand, differences in the chemical nature and the pore size of packings, or in the hydrophobicity of the eluting solvent, had little effect on DNA retardation. Size-dependent fractionation of DNA was also achieved even on columns packed with nonporous packings having anionic groups (cation exchangers). In conclusion, these results confirmed the previous conclusion that slalom chromatography is not based on an adsorption or equilibrium phenomenon but should be attributed to a hydrodynamic phenomenon.
Animals↗
Lack of enhancing effects of fenvalerate and esfenvalerate on induction of preneoplastic glutathione S-transferase placental form positive liver cell foci in rats.
The modifying effects of fenvalerate and esfenvalerate administration on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given fenvalerate at dietary levels of 1500, 500, 150, 50 and 15 parts per million (ppm), esfenvalerate at 500 ppm, or 2-acetylamino-fluorene (2-AAF) at 200 ppm and sodium phenobarbital (PB) at 500 ppm as positive controls for 6 weeks. At week 3 following DEN administration, all animals were subjected to partial hepatectomy. Prominent neurologic signs and moderate retardation of body weight were observed in the groups given 1500 ppm fenvalerate and 500 ppm esfenvalerate, although no adverse effects on survival were evident. While statistically significant increases in relative liver weights were noted in rats given fenvalerate at doses of 1500 or 500 ppm, no toxic hepatocyte lesions were found. Neither fenvalerate nor esfenvalerate significantly increased the numbers or areas of glutathione S-transferase placental form (GST-P) positive liver cell foci observed after DEN initiation, in clear contrast to the positive controls, 2-AAF and PB. The results thus demonstrated that fenvalerate and esfenvalerate are non-toxic for rat hepatocytes and lack modifying potential for liver carcinogenesis in our medium-term bioassay system.
2-Acetylaminofluorene↗
Effects of phorbol ester on cell growth inhibition by transforming growth factor beta 1 in human hepatoma cell lines.
The effects of phorbol ester on cell growth inhibition by transforming growth factor beta 1 (TGF-beta 1) in human hepatoma cell lines, Mahlavu and PLC/PRF/5, were investigated. TGF-beta 1 (2.5 to 10 pM) alone could not inhibit the growth of Mahlavu cells, whereas in the presence of 12-O-tetradecanoyl phorbol 13-acetate (TPA) at 1 ng/ml, TGF-beta 1 could suppress their growth in a dose-dependent manner. The growth of PLC/PRF/5 cells could be inhibited by addition of TGF-beta 1 (2.5 to 10 pM) alone in a dose-dependent manner, and this action was not affected by TPA (1 ng/ml). The TGF-beta 1 inhibition induced by TPA in Mahlavu cells could not be cancelled by addition of protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) (10 microM) or staurosporin (1 nM). Thus, TPA could induce TGF-beta 1 inhibition of cell growth in Mahlavu cells which did not respond to TGF-beta 1 alone, and activation of protein kinase C does not seem to be behind this TPA action.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Increase in the active form of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human hepatocellular carcinoma: possible mechanism for alteration of cholesterol biosynthesis.
3-Hydroxy-3-methylglutaryl coenzyme A reductase activity and the rate of sterol biosynthesis are positively correlated with DNA synthesis and proliferation of mammalian cells. The total (active plus latent) activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and the activity of its active form in hepatocellular carcinoma (HCC) from seven patients were measured and compared with those in liver tissue from five control subjects. The activity of the active form in HCC was 61 +/- 21 (SD) pmol/min/mg microsomal protein, while it was only 17 +/- 9.8 pmol/min/mg protein in the liver tissue from the controls; the difference was significant (P less than 0.005). The total activity of the reductase was also higher in HCC although the difference was not significant. The microsomal contents of the enzyme protein also were not significantly different. The rate of cholesterol biosynthesis was 307 +/- 81 pmol/h/mg tissue in HCC and 79.6 +/- 52 in normal liver tissue, indicating a significant increase in the rate in HCC (P less than 0.001). Thus, enhanced synthesis of cholesterol in human HCC seems to result partly from an increase in the active form of the reductase.
Carcinoma, Hepatocellular↗
Carcinogenicity and modification of carcinogenic response by antioxidants.
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Animals↗
Difference in the ability of blood group-specific lectins and monoclonal antibodies to recognize the ABH antigens in human tissues.
Twelve different kinds of blood group-specific lectins have been used along with monoclonal anti-A, -B and -H antibodies for detecting the corresponding antigens in selected human tissues. Although most of the lectins recognized the antigens in the tissue sections examined, they displayed marked differences in their recognition patterns in certain tissues. Helix asparsa agglutinin (HAA), Helix pomatia agglutinin (HPA) and monoclonal anti-A antibody recognized A antigens in the mucous cells of salivary glands from blood group A or AB nonsecretor as well as secretor individuals, whereas Dolichos biflorus agglutinin (DBA), Griffonia simplicifolia agglutinin-I (GSA-I), Sophora japonica agglutinin (SJA) and Vicia villosa agglutinin (VVA) did not bind to them from nonsecretors. A antigens in endothelial cells, lateral membrane of pancreatic acinar cells and small mucouslike cells of submandibular glands from some individuals were likewise recognized by HAA and HPA but not by other blood group A-specific lections. In contrast, both HAA and HPA did not recognize the A antigens in mucous cells of Brunner's glands while other A-specific lectins and monoclonal anti-A antibody reacted specifically with the antigens. Such a difference was not observed with lectins specific for blood group B. However, the B antigens in Brunner's glands were recognized by these lectins but not with monoclonal anti-B antibody. The difference in labelling ability was also noted among the blood group H-specific lectins and monoclonal anti-H antibody in endothelial cells of blood vessels. Ulex europaeus agglutinin-I reacted with these cells irrespective of ABO and the secretor status of the individuals, while Anguilla anguilla agglutinin and monoclonal anti-H antibody reacted only with those cells from blood group O individuals. No reaction was observed with Lotus tetragonolobus agglutinin in these tissue sites. These results suggest a great diversity of blood group antigens in different human tissues.
ABO Blood-Group System↗
Relationship between lectin binding properties and the expression of blood group ABH antigens in vascular endothelia and red blood cells from 18 primate species.
The reactivity was examined of horseradish peroxidase labelled Ulex europaeus agglutinin-I (UEA-I) and Griffonia simplicifolia agglutinin I-B4 (GSAI-B4) with red blood cells and vascular endothelium in formalin-fixed, paraffin embedded tissues from 18 primate species. The expression of blood group ABH antigens in these cells as well as secretions from other tissues was also examined by the indirect immunoperoxidase method using monoclonal anti-ABH antibodies as primary antibodies. In Prosimians and New World monkeys which lack ABH antigens on both red blood cells and endothelial cells, but produce these antigens in other tissue secretions, GSAI-B4 always reacted with both red blood cells and endothelial cells. In Old World monkeys, which express blood group antigens on endothelial cells but not on red blood cells, neither GSAI-B4 nor UEA-I reactivity were observed, except the endothelial cells from blood group B or O individuals occasionally reacted with GSAI-B4 or UEA-I, respectively. Although UEA-I reactivity was not observed in the endothelial cells of gibbon, it reacted with these cells from chimpanzees. In these two anthropoid apes, both endothelial cells and red blood cells expressed ABH antigens as in humans. These results suggest the close evolutionary relationship between the expression of blood group ABH antigens and lectin binding properties of red blood cells and endothelial cells in primate species.
ABO Blood-Group System↗
The role of neostigmine in development of acute gastric mucosal lesion in dogs with live bacterial flora-induced shock.
The factors that frequently cause the development of acute gastric mucosal lesions (AGML) were studied in 37 mongrel dogs. Bacterial shock was induced by bolus injection of E. coli live bacterial flora (10(10) cells/kg body weight) under parietal cell-stimulated condition by intravenous administration of 0.008 mg/kg per hour of pentagastrin. In addition, 0.01 mg/kg per hour of neostigmine sulfate was administered intravenously during the experiment. Frequent development of AGML was observed in the neostigmine-administered canines without significant changes in the gastric corporal and antral tissue blood flow. In the neostigmine-administered group, AGML was observed in the antrum, although in the other group AGML was mostly observed in the corpus. These results suggest that a neostigmine-induced systemic vagostimulated condition by intravenous administration of neostigmine plays an important role in the development of AGML in dogs subjected to bacterial shock.
Animals↗
Carcinogenicity study of methyl hesperidin in B6C3F1 mice.
A long-term carcinogenicity study of methyl hesperidin, a compound of the vitamin P group, was carried out in B6C3F1 mice receiving dietary concentrations of 0, 1.25 or 5%. Administration was continued for 96 wk and then the mice were maintained on basal diet for an additional 8 wk. Growth retardation during the experiment with final changes in organ weights were observed in females given the 1.25% dose of methyl hesperidin and in both sexes receiving the 5.0% treatment. However, no biologically significant effects were evident with respect to mortality or clinical signs. Furthermore, treatment with methyl hesperidin did not result in any changes in haematology, clinical chemistry and urinalysis data. On histological examination, no significant alteration of non-neoplastic and neoplastic lesion incidence was observed in treated mice. The results thus demonstrated that methyl hesperidin lacked any carcinogenicity for B6C3F1 mice in the 96-wk feeding regimen used in this study.
Administration, Oral↗
Modulatory interaction between initial clofibrate treatment and subsequent administration of 2-acetylaminofluorene or sodium phenobarbital on glutathione S-transferase positive lesion development.
The effects of 2-acetylaminofluorene (2-AFF) or sodium phenobarbital (PB) treatment subsequent to clofibrate (CF) administration in terms of preneoplastic lesion development and induction of hepatocellular carcinomas (HCC) were studied using Fischer 344 rats. Animals received CF (0.3% in diet) for the initial 30 weeks, and then either 2-AAF (0.01% in diet), PB (0.05% in diet) or basal diet until week 78. Further groups were initially given basal diet, and then treated with 2-AAF or PB week 30. Two-thirds partial hepatectomy was carried out on all animals at week 3, sacrifice of representative groups being performed at weeks 30, 48 and 78. No glutathione S-transferase placental form positive (GST-P+) or negative focal or nodular lesions were apparent at the cessation of CF administration. The induction of GST-P+ focal lesions by 2-AAF was markedly decreased at week 48 in the group previously given CF (P less than 0.05) and furthermore, the respective incidences of HCC at week 78 were 4/17 (23.5%) in the CF----2-AAF group and 7/17 (41.2%) in the 2-AAF alone case. No significant differences between CF----PB and PB alone groups were evident with regard to either GST-P+ lesions and HCC at weeks 48 and 78. No CF-specific GST-P negative neoplastic nodules or HCC were observed in any of the experimental groups. These results suggest that pretreatment with CF may inhibit the induction of GST-P+ focal lesions and HCC by subsequently administrated 2-AAF and that CF demonstrates no initiating activity for liver carcinogenesis under the present condition.
2-Acetylaminofluorene↗
Promoting action of prolactin released from a grafted transplantable pituitary tumor (MtT/F84) on rat prostate carcinogenesis.
The potential modifying effects of high prolactinemia on rat prostate carcinogenesis was investigated. Male F344 rats were treated at 5 times of 5-week intervals with s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB), each injection following 3 weeks pretreatment with dietary ethinyl estradiol. After completion of the carcinogen administration stage, rats received multiple s.c. transplantations of a prolactin producing transplantable pituitary tumor, MtT/F84 until sacrifice at week 51. The effects of additional or single treatment with bromocriptine, a prolactin suppressing agent, were also investigated. The body, liver and kidney but prostate weights were significantly increased in the groups given MtT/F84. Although the development of prostate carcinomas was not affected by the observed hyperprolactinemia, the incidences of atypical hyperplasia of both ventral and lateral prostate were significantly enhanced. The findings thus indicate that prolactin may have promoting potential for prostate carcinogenesis.
Aminobiphenyl Compounds↗
Structural analysis of galactose oxidase.
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Base Sequence↗
Lack of hepatotoxicity or promotion of enzyme-altered liver foci development in rats treated with harman or norharman.
The modifying effects of harman or norharman on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given harman or norharman at dietary levels of 1000 and 200 parts per million (ppm), or sodium phenobarbital (PB) at 500 ppm as a positive control, for 6 wk. At wk 3 following DEN administration, all animals were subjected to partial hepatectomy. Marked retardation of body weight gain was observed in rats treated with harman or norharman at 1000 ppm, but not at 200 ppm. Increased relative kidney but not liver weights were associated with harman or norharman treatment, especially in the higher dose groups. Although no toxicity-related hepatocyte lesions were found, severe renal toxic tubular lesions and regeneration were evident. Neither harman nor norharman significantly increased the numbers or areas of glutathione S-transferase placental form (GST-P) positive foci observed after DEN initiation, in clear contrast to PB. The results thus demonstrated that harman and norharman are nontoxic for the liver and lack modifying potential for liver carcinogenesis in our medium-term bioassay system.
Alkaloids↗
Para-methoxyphenol strongly stimulates cell proliferation in the rat forestomach but is not a promoter of rat forestomach carcinogenesis.
The modifying effects of para-methoxyphenol (PMP) second stage treatment on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated rat forestomach carcinogenesis were investigated. Groups of 15 6 week old male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later were administered powdered diet containing 2.0, 1.0, 0.5, 0.25 or 0% PMP until they were killed at week 52. PMP caused epithelial damage and hyperplasia in a dose-dependent manner in the forestomach epithelium, but nevertheless was not associated with any increase in the incidence of either papillomas or squamous cell carcinomas. The results thus clearly indicated that stimulation of cell proliferation does not necessarily correlate with promotion in the second stage of two-stage forestomach carcinogenesis.
Animals↗