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Biomedical subjects

N Ito

Publications and source records attributed to N Ito.

At least 361 records · Page 20Linked to original sources
PubMed1992

Effect of acyl derivatives of 4,4,4-trifluoro-1-phenyl-1,3-butanedione on 2-acetylaminofluorene-induced glutathione S-transferase positive foci in the rat liver.

Acyl derivatives of 4,4,4-trifluoro-1-phenyl-1,3-butanedione (TFPB), 1-benzoyl-2-trifluoromethyl-2-acetoxyethene (BTAE), and 1-benzoyl-2-trifluoromethyl-2-(4-methylthio)benzoyloxyethene (BTME), were synthesized and investigated for inhibition of tRNA binding by N-acetoxy-2-acetylaminofluorene (N-AcO-AAF), and induction of glutathione S-transferase placental form (GST-P) positive foci in the rat liver by 2-acetylaminofluorene (2-AAF). Male F344 rats were given BTAE or BTME intraperitoneally and 2-AAF by intragastric intubation. Two weeks following the treatment, the rats were maintained on the diet containing 0.05% phenobarbital for an additional 6 weeks and then killed. Development of GST-P positive foci was not affected by concomitant treatment with BTAE or BTME. These two compounds inhibited the in vitro binding of N-AcO-AAF to tRNA. Thus, although these diacylmethane derivatives had the in vitro inhibitory activity, they did not inhibit tumor-initiating activity of 2-AAF in the rat liver.

2-Acetylaminofluorene↗
PubMed1992

Analysis of carcinogenic activity of some pesticides in a medium-term liver bioassay in the rat.

Eight pesticides were tested in a medium-term bioassay based upon the induction of preneoplastic lesions in the liver. Rats were initially given diethylnitrosamine intraperitoneally at a dose of 200 mg/kg body weight and 2 weeks later were treated with the pesticides for 6 weeks and then killed; all rats had a partial hepatectomy at week 3. Hepatocarcinogenic potential was assessed by comparing the number and area of glutathione S-transferase placental form positive foci in the liver with those of controls given diethylnitrosamine (DEN) alone. Positive results were seen with p,p-DDT and Triadimefon. Permethrin (mixture of 39% cis form and 61% trans form) showed borderline results. Permethrin (25/75), Deltamethrin, Cypermethrin (52/48), while Trimorphamide and Propineb gave negative results. Our findings provide experimental evidence to indicate that compounds active in this assay have a potential for liver carcinogenicity in rodents.

Animals↗
PubMed1992

Animal prostate carcinoma models: limited potential for vertebral metastasis.

Several methods for induction of rat prostate carcinomas are now available. The induced adenocarcinomas, which develop normally in the lateral and/or dorsal prostate, are invasive and can form distant metastases. Metastatic sites include the abdominal cavity, liver, lung, and/or lymph nodes but, as yet, bone metastasis of prostate cancers in experimental animals has not been reported, despite its being very common in man. Anatomical and hemodynamic differences seem to be account for this lack of bone metastasis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Enhancement of host resistance to opportunistic infections by ubenimex (bestatin).

Ubenimex is a low molecular biological response modifier (BRM) which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the effect of ubenimex on infection with Candida albicans was investigated in normal and immunosuppressed mice, and it showed a prophylactic effect. In normal mice, ubenimex prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with cyclophosphamide 4 days before infection, ubenimex at 5 mg/kg for 5 days significantly increased the number of survivors. Significant improvement in peritoneal leukocyte counts and in function of neutrophils including phagocytosis and release of activated oxygen was observed in ubenimex-treated mice. These results indicate that ubenimex is a potent BRM for prevention against opportunistic infections.

Animals↗
PubMed1992

Spinal cord vascular and leptomeningeal amyloid beta-protein deposition in a case with cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid fibrils on leptomeningeal and cortical blood vessels, and the incidence of this disorder increases with age. However, this form of vascular amyloid deposition rarely involves tissues outside of the brain. A 71-year-old woman first developed some deterioration in memory, and soon afterwards suffered from recurrent episodes of subcortical hemorrhage. Histopathological examination of this case revealed typical pathology of Alzheimer's disease with an extensive appearance of beta-protein type CAA, and additionally, the spinal leptomeningeal vessels and the pia-arachnoid membranes were also affected by amyloid beta-protein deposits. The spinal cord involvement associated with CAA and Alzheimer's disease is unusual, and the present case provides additional important information on the pathogenesis of disorders with beta-protein deposition including Alzheimer's disease.

Aged↗
PubMed1992

Effects of hickory-smoke condensate on development of pepsinogen 1-altered pyloric glands in rats.

Hickory-smoke condensate (HSC) is a popular food flavouring in the USA. Available data have suggested that this food additive has tumour-initiating/promoting potential. Accordingly, a commercial HSC has been investigated for its capacity to promote tumours in the rat glandular stomach using pepsinogen 1 (Pg 1)-altered pyloric glands (PAPG) as the marker of preneoplastic lesions. The development of PAPG initiated by a single intragastric administration of N-methyl-N'-nitroso-N-nitrosoguanidine was significantly increased by feeding rats a diet containing 5% HSC; no effect was observed with lower doses (1.25 or 2.5%) of HSC. The results suggest that HSC has weak tumour-promoting potential in the rat glandular stomach.

Animals↗
PubMed1992

Lack of carcinogenicity of tragacanth gum in B6C3F1 mice.

Tragacanth gum was administered at dietary levels of 0 (control), 1.25 and 5.0% to groups of 50 male and 50 female B6C3F1 mice for 96 wk after which all animals were maintained on a basal diet without tragacanth gum for a further 10 wk. Mean body weights of females in the 5.0% and 1.25% groups were lower than those of the controls after 11 and 16 wk, respectively. However, there were no treatment-related clinical signs or adverse effects on survival rate, urinalysis, haematology, blood biochemistry and organ weight. While detailed histopathology revealed the development of squamous cell hyperplasias, papillomas and one carcinoma in the forestomach, there was no significant treatment-related increase in the incidence of any preneoplastic or neoplastic lesion. Thus, under the experimental conditions used, tragacanth gum was not carcinogenic in B6C3F1 mice of either sex.

Animals↗
PubMed1992

Liver medium-term bioassay in rats for screening of carcinogens and modifying factors in hepatocarcinogenesis.

The present report describes a study of the hepatocarcinogenic potential of a second large assay series of 94 compounds carried out using the rapid bioassay system (DEN-PH model) developed in this laboratory and based on the two-step concept of hepatocarcinogenesis. Male F344 rats were initially given a single dose of diethylnitrosamine (DEN, 200 mg/kg body weight ip) and, starting 2 wk later, were treated with test compounds for 6 wk and then killed, all rats being subjected to a two-thirds partial hepatectomy at wk 3. Carcinogenic potential was scored by comparing the numbers (no./cm2) and areas (mm2/cm2) of induced glutathione S-transferase placental form (GST-P) positive foci in the livers of groups of about 15 rats with those of corresponding control groups given DEN alone. Positive was scored for a significant increase (P < 0.05) in quantitative values of GST-P positive foci, negative for no change or a decrease. Results for the 94 compounds were also compared with previously published data from Salmonella/microsome (Ames) tests and long-term carcinogenicity studies in rats and mice. Of the known liver carcinogens, 14 out of 14 (100%) mutagenic (Ames test) compounds and 10 out of 12 (83%) non-mutagenic compounds gave positive results in our DEN-PH system (mean 92%). Two hepatocarcinogenic peroxisome proliferators did not enhance the development of GST-P positive foci. Carcinogens other than hepatocarcinogens gave fewer positive results (five out of 17, 29%). One of the 13 compounds reported as non-carcinogenic, malathion, gave positive results in the DEN-PH assay, suggesting that this compound is a weak hepatocarcinogen or tumour promoter for hepatocarcinogenesis based on the two-stage hypothesis for carcinogenesis. The present study also provided information regarding the inhibitory potential of nine compounds. The practical usefulness and benefits of the DEN-PH protocol for the rapid screening of carcinogenic agents are discussed.

Animals↗
PubMed1992

Pathological markers for non-genotoxic agent-associated carcinogenesis.

A variety of positive or negative enzyme altered foci have been proposed as preneoplastic marker lesions in the rat liver. Frozen sections are required in some cases. We have compared the suitability of various histochemically or immunohistochemically demonstrated markers and concluded that immunohistochemically-stained glutathione S-transferase placental form (GST-P) positive foci are particularly useful for practical application in risk assessment. Advantages include ease of quantitative foci analysis on a number of samples since acetone or formalin-fixed paraffin blocks can be used and clear contrast of foci against the surrounding liver tissue facilitates recognition. We have established a liver medium-term bioassay model of 8 weeks' duration using diethylnitrosamine as an initiator and GST-P positive foci as the endpoint lesions. At present, 58 non-genotoxic chemicals for which carcinogenicity data are available have been examined and many carcinogenic agents, mostly liver carcinogens, have been satisfactorily detected as having carcinogenic potential. Exceptional examples are two peroxisome proliferators, clofibrate and DEHP. For these chemical, several peroxisomal enzymes such as catalase and enoyl CoA hydratase have been tested as markers.

Animals↗
PubMed1992

Histochemical and cytochemical localization of blood group antigens.

The oligosaccharide structures of blood group antigens are not the primary gene products; they are constructed in a stepwise manner by adding particular sugar to precursor oligosaccharides via several glycosyltransferases coded for by different blood group genes (Watkins 1966, 1978, 1980). Consequently, final profiles of antigens expressed in each cell type are influenced by many different factors such as the intrinsic composition of glycosyltransferase species which are defined by the genotype of the individuals, relative activity or amount of these enzymes (repression, derepression or induction of the enzymes), competition between enzymes with overlapping substrate specificity, the organization of the enzymes in membranes, utilizability of precursors and specific substrate sugars, and the activity level of degradating enzymes. Changes in the antigen profiles during maturation, differentiation and malignant transformation are thought to be intimately related to the variability of these factors. Although great importance attaches to histo- and cytochemical information on the distribution and levels of glycosyltransferases and messenger RNA corresponding to the relevant enzyme, detailed and precise localization of the blood group antigens and their variants is the base line for analyzing these complex factors. On the basis of individual genotype and histochemical findings about the antigen distribution and the interrelationship between cells and cellular components producing different antigenic structures (cellular and subcellular mosaicism), we can deduce precursor oligosaccharide levels as well as the status of gene activation and its primary product, glycosyltransferases. Thus, these findings are a prerequisite for further analysis at the molecular genetic level. As emphasized in this article, lectin staining or immunostaining methods with MAbs combined with glycosidase digestion procedures are powerful tools for in situ analysis of carbohydrate structures in histochemical systems. Although in some cases valuable results have been obtained by applying the technique, our knowledge concerning the distribution of complex carbohydrate structures is still far from satisfactory. Along with well defined MAbs and lectins, the key to developing our methods further is successful introduction of glycosidases, in particular, endoglycosidases since these reagents are indispensable for analyzing the inner core structures and glycoconjugate species of the blood group antigens. Application of these techniques at the ultrastructural level is an alluring possibility, even though many difficulties must be overcome. Although their functional roles have not yet been determined, a diverse array of macromolecules is known to be decorated with blood group-related antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Three-dimensional structure of galactose oxidase: an enzyme with a built-in secondary cofactor.

Galactose oxidase is a copper-containing enzyme, which catalyses stereospecific oxidation of primary alcohols. The three-dimensional structure of the enzyme has been determined in this study by X-ray crystallography at high resolution. The molecule is almost entirely composed of beta-structures and consists of three domains. The arrangement of 28 beta-strands in the second domain is of particular interest, having seven four-stranded antiparallel beta-sheets with pseudo-sevenfold symmetry. The copper site has square-pyramidal coordination with two histidines, one tyrosine and one exogenous ligand at the equatorial sites and another tyrosine at the axial site. The most intriguing structural feature is a covalent bond between C epsilon 1 of Tyr-272, which is one of the equatorial ligands, and S gamma of Cys-228. This unexpected thioether bond, and Trp-290 stacked above it, strongly supports the presence of a tyrosine free radical in the enzyme as a 'built-in' secondary cofactor. Calculation of the molecular surface shows a small pocket at the copper site and suggests a substrate-binding model, which can explain the substrate specificity. A model for the catalytic mechanism, involving a tyrosine free radical and basic tryptophan, is also proposed.

Amino Acid Sequence↗
PubMed1992

Influence of caffeic acid and other o-dihydroxybenzene derivatives on N-methyl-N'-nitro-N-nitrosoguanidine-initiated rat forestomach carcinogenesis.

Promotion effects of the o-dihydroxybenzene derivatives, protocatechuic acid (PCA), dopamine hydrochloride (DAH), dl-dopa and caffeic acid on forestomach and glandular stomach carcinogenesis were investigated in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 20 male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later than received diet containing 1.5% PCA, 1.5% DAH, 1.5% dl-dopa or 1% caffeic acid or basal diet alone for 51 weeks and then killed. Other groups of 10-15 rats were given PCA, DAH, dl-dopa or basal diet alone without the MNNG pretreatment. On histological assessment, the incidences of forestomach papillomas and squamous cell carcinomas were significantly enhanced in the group treated with caffeic acid (95 and 100%) as compared with the control values (35 and 10%). Although the incidence was not different, the number of papillomas per rat in the group given DAH (0.79 +/- 0.79) was also significantly increased (0.35 +/- 0.49). PCA and dl-dopa treatments did not modify the development of neoplastic lesions in the forestomach epithelium to any significant extent. None of the four chemicals enhanced glandular stomach carcinogenesis. The results thus demonstrated that whereas caffeic acid and DAH respectively, exert strong and weak promotion activity for rat forestomach carcinogenesis this promotion potential is not shared by all dihydroxybenzene derivatives. An influence of substituents in the para position in addition to the o-dihydroxy moiety is indicated.

Adenocarcinoma↗
PubMed1992

Effect of dietary fiber on cytochrome P450IA1 induction in rat colonic mucosa.

The effect of dietary fiber on the induction of cytochrome P450IA1 in rat colonic mucosa after a single intragastric injection of 3-methylcholanthrene (3MC, 20 mg/kg) was investigated by examining the drug-metabolizing enzyme activity, immunoblotting for cytochrome P450IA1 and immunohistochemistry. 7-Ethoxycoumarin-O-deethylase activities were approximately 20-fold higher in microsomes from both proximal and distal portions of the colonic mucosa of control diet-fed 3MC-treated rats compared with those of control diet-fed untreated rats. Strong immunofluorescence for cytochrome P450IA1 was localized in the cytoplasm of the colonic mucosa surface epithelium from the control diet-fed 3MC-treated rats. 7-Ethoxycoumarin-O-deethylase activity and cytochrome P450IA1 content determined by immunoblotting were significantly lower in wheat bran-fed 3MC-treated rats than in control diet-fed 3MC-treated rats. Immunohistochemical analysis showed much weaker immunofluorescence for cytochrome P450IA1 in the surface epithelium of the colonic mucosa of the wheat bran-fed 3MC-treated rats. These observations suggested that dietary fiber can affect the induction of cytochrome P450IA1 in colonic mucosa by dietary inducers or carcinogens.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1992

Repeated exposure to Opisthorchis viverrini and treatment with the antihelminthic Praziquantel lacks carcinogenic potential.

The effects of repeated Praziquantel administration, subsequent to infection and reinfection with Opisthorchis viverrini (OV), on lesion development in the Syrian hamster liver were investigated. Five applications of the antihelminthic drug were made (300 mg/kg body wt, i.g.), each time approximately 5 weeks after dosing with 60-80 OV metacercariae at weeks 0, 8, 16, 24 and 32. The animals were then maintained until week 40 when they were killed; histopathological investigation revealed no significant development of either hepatocellular of cholangiocellular preneoplastic/neoplastic lesions. The results indicate that repeated exposure to Praziquantel at levels sufficient for successful removal of parasite infestation does not itself carry carcinogenic risk.

Animals↗
PubMed1992

Enhancement of GST-P-positive liver cell foci development by nivalenol, a trichothecene mycotoxin.

In order to elucidate whether T-2 toxin (T-2) and nivalenol (NIV), the naturally occurring trichothecene mycotoxins in food and feed, are carcinogenic or possess an ability to modulate aflatoxin B1 (AFB1)-induced hepatocarcinogenicity, a medium-term liver bioassay was carried out. F344 male rats were given a single i.p. injection of diethylnitrosamine (DEN, 200 mg/kg), and then fed the test trichothecenes in diet (2 and 5 p.p.m. T-2 or 6 p.p.m. NIV) for 6 weeks beginning 2 weeks after the injection. Some control groups received DEN alone. For synergism between AFB1 and the trichothecenes, DEN-initiated rats as above were given a single i.p. injection of AFB1 (0.5 mg/kg) 2 weeks later and were fed a NIV-containing diet (6 p.p.m.) for 6 weeks. The other control group received the vehicle alone. Control rats not initiated with DEN were also treated with AFB1, NIV or T-2 alone as above. All rats were subjected to a two-thirds partial hepatectomy (PH) at week 3 and killed at week 8, and liver sections were analyzed by glutathione S-transferase placental form (GST-P) expression. In rats that did not receive DEN, AFB1 alone enhanced both the numbers and areas of GST-P-positive foci as reported earlier, while NIV or T-2 alone induced no marked changes. In rats initiated with DEN, AFB1 caused a marked expression of GST-P, and thus the hepatocarcinogenicity of AFB1 was reconfirmed. The expression of GST-P foci in rats fed T-2 or NIV was found to be at background level, indicating that the hepatocarcinogenicity was not predicted for the trichothecene mycotoxins such as T-2 and NIV by this medium-term bioassay system. In the group initiated by DEN followed by AFB1, on the other hand, an elevation of both the numbers and areas of GST-P-positive foci was observed by the subsequent feeding of rats with NIV, and this elevation was statistically significant from the sum totals of individual data of AFB1 or NIV alone. From this evidence, it is predicted that NIV causes an enhancing effect on AFB1-induced hepatocarcinogenesis.

Animals↗
PubMed1992

Dose-dependent formation of preneoplastic foci and DNA adducts in rat liver with 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

Dose responses to two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in induction of glutathione S-transferase placental form positive liver cell foci (GST-P+ foci) and DNA adduct formation in the liver were examined in male F344 rats. Beginning 2 weeks after a single diethylnitrosamine (DEN) injection (200 mg/kg, i.p.), rats received MeA alpha C or PhIP in the diet at various doses for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) 1 weeks after the test agents were added to the diet and were killed 8 weeks after DEN initiation. MeA alpha C (100, 200, 400 and 800 p.p.m.) significantly increased numbers and areas of GST-P+ foci over control levels in all dose groups with a clear dose-response. In contrast, PhIP (50, 100, 200 and 400 p.p.m.) only equivocally increased foci development in the highest dose group and rather was associated with decrease in the lower dose groups. DNA adduct formation assessed by 32P-postlabeling demonstrated a dose-dependent increase with both chemicals, the levels being much higher with MeA alpha C. Thus, two highly mutagenic heterocyclic amines that are produced in broiled foodstuffs exerted different influence on GST-P+ foci development and DNA adduct formation; these findings are consistent with liver carcinogenicity in rats and/or mice.

Animals↗
PubMed1992

Enhancing effects of diallyl sulfide on hepatocarcinogenesis and inhibitory actions of the related diallyl disulfide on colon and renal carcinogenesis in rats.

It has been reported that diallyl sulfide (DS) and diallyl disulfide (DDS), major volatile compounds in garlic (Allium sativum), exert anticarcinogenic activity in several organs in rodents. The modifying effects of these two chemicals were therefore assessed using two-step liver and multi-organ carcinogenesis models. In experiment 1, male F344 rats were given a single i.p. injection of N-diethylnitrosamine (200 mg/kg body wt) and then received DS or DDS by intragastric intubation at doses of 200 and 50 mg/kg body wt, respectively, three times a week for 6 weeks. All rats were subjected to two-thirds partial hepatectomy at experimental week 3. In experiment 2, male F344 rats were sequentially treated with five carcinogens with different organ target sites for 4 weeks, and then administered DS or DDS as in experiment 1 for 24 weeks. DS demonstrated clear enhancing effects on the development of glutathione S-transferase placental form positive foci in both experiments. On the other hand, an inhibitory potential in colon and renal carcinogenesis was observed in rats treated with DDS. Therefore, while DDS may act as a chemopreventive agent, DS may promote hepatocarcinogenesis.

Allyl Compounds↗