Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 559 records · Page 31Linked to original sources

PubMed1995

Chemoprevention of azoxymethane-induced colon carcinogenesis by dietary feeding of S-methyl methane thiosulfonate in male F344 rats.

Modifying effects of dietary exposure of S-methyl methane thiosulfonate (MMTS) isolated from cauliflower Brassica oleracea L. var. botrytis on rat colon carcinogenesis induced by azoxymethane (AOM) and on the expression of cell proliferation biomarkers were investigated in two experiments. In experiment 1, male F344 rats were given three s.c. injections of AOM (15 mg/kg body weight) and fed 100 ppm MMTS for 5 weeks, starting 1 week before the first dose of AOM. The frequency of colonic aberrant crypt foci was determined at 5 weeks after the start. Feeding of 100 ppm MMTS for 5 weeks significantly decreased the number of aberrant crypt foci/colon. Colonic mucosal ornithine decarboxylase activity and the number of silver-stained nucleolar organizer regions per nucleus in colonic epithelium were significantly decreased by MMTS treatment compared with those of AOM alone. In experiment 2, effects of dietary feeding of MMTS at two doses (20 and 100 ppm) during the postinitiation phase on intestinal tumorigenesis initiated with AOM were investigated by using a long-term experiments in male F344 rats. Incidence of intestinal neoplasms of rats fed MMTS-containing diets after AOM exposure were reduced in a dose-dependent manner. Feeding of MMTS during the postinitiation phase decreased the number of aberrant crypt foci/colon, colonic ornithine decarboxylase activity, 5-bromodeoxyuridine-labeling index in colonic epithelium, and polyamine level in blood compared with those of AOM alone. These results suggest that MMTS might be a possible chemopreventive agent for intestinal neoplasia.

Animals↗

PubMed1995

Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls, astaxanthin and canthaxanthin.

The chemopreventive effects of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) on oral carcinogenesis induced by 4-nitroquinoline 1-oxide (4-NQO) was investigated in male F344 rats. Rats were given 20 ppm of 4-NQO in their drinking water for 8 weeks to induce oral neoplasms or preneoplasms. Animals were fed diets containing 100 ppm AX or CX during the initiation or postinitiation phase of 4-NQO-induced oral carcinogenesis. The others contained the groups of rats treated with AX or CX alone and untreated. At the end of the study (week 32), the incidences of preneoplastic lesions and neoplasms in the oral cavity of rats treated with 4-NQO and AX or CX were significantly smaller than those of rats given 4-NQO alone (P < 0.001). In particular, no oral neoplasms developed in rats fed AX and CX during the 4-NQO exposure and in those given CX after the 4-NQO administration. Similarly, the incidences of oral preneoplastic lesions (hyperplasia and dysplasia) in rats treated with 4-NQO and AX or CX were significantly smaller than that of the 4-NQO-alone group (P < 0.05). In addition to such tumor inhibitory potential, dietary exposure of AX or CX decreased cell proliferation activity in the nonlesional squamous epithelium exposed to 4-NQO as revealed by measuring the silver-stained nucleolar organizer regions protein number/nucleus and 5'-bromodeoxyuridine-labeling index. Also, dietary AX and CX could reduce polyamine levels of oral mucosal tissues exposed to 4-NQO. These results indicate that AX and CX are possible chemopreventers for oral carcinogenesis, and such effects may be partly due to suppression of cell proliferation.

Animals↗

PubMed1995

Phosphorylation of proteasome substrate by a protein kinase associated with the 26 S proteasome is linked to the ATP-dependent proteolysis of the 26 S proteasome.

A protein kinase phosphorylating the 45-kDa proteasome subunit was co-purified with the 26 S proteasome from the porcine heart. This kinase appears to be associated with the 26 S proteasome, since the kinase activity was co-eluted with the 26 S proteasome on Superose 6 FPLC and immunoprecipitated with anti-20 S proteasome antibody. This kinase also phosphorylated the casein. Furthermore, the phosphorylated casein was more efficiently hydrolyzed by the 26 S proteasome than the dephosphorylated casein without ATP. Inhibition patterns of kinase inhibitors against the 45 kDa subunit and casein were well in accord with the inhibition pattern against the ATP-dependent proteolysis of the 26 S proteasome, suggesting that the phosphorylation of casein by a protein kinase associated with the 26 S proteasome is linked to the ATP-dependent proteolysis of the 26 S proteasome.

Adenosine Triphosphate↗

PubMed1995

Anti-CD9 monoclonal antibody activates p72syk in human platelets.

NNKY 1-19, anti-CD9 monoclonal antibody (MoAb), induced protein tyrosine phosphorylation of 125-, 97-, 75-, 64-, and 40-kDa proteins in human platelets, whereas F(ab')2 fragments of NNKY 1-19 did not, suggesting that the stimulation of Fc gamma II receptors is required for the induction of protein tyrosine phosphorylation. Tyrosine-phosphorylated proteins of 97 and 125 kDa were associated with aggregation, while NNKY 1-19-induced protein tyrosine phosphorylation was completely inhibited by prostaglandin I2 (PGI2). The activity of p72syk was assessed in immunoprecipitation kinase assays to determine at which step the signal transduction pathway leading to protein tyrosine phosphorylation was suspended. NNKY 1-19 induced a rapid and transient increase in the p72syk-associated tyrosine kinase activity that peaked at 10 s and subsided to the original level 2 min after stimulation. Coinciding with this time course, p60c-src transiently associated with p72syk. In platelets preexposed to GRGDS peptides or PGI2, NNKY 1-19 also increased the p72syk-associated tyrosine kinase activity and led to the association of p60c-src with p72syk. However, in contrast to the control without any inhibitor, the elevated tyrosine kinase activity and the associated state of the two tyrosine kinases persisted as long as 5 min after stimulation. F(ab')2 fragments of NNKY 1-19 induced changes similar to those observed with the effects of GRGDS peptides or PGI2 treatment on intact IgG NNKY 1-19 stimulation. F(ab')2 fragments of another CD9 MoAb, PMA2, had effects on p72syk essentially similar to those of NNKY 1-19. These findings suggest that the binding of anti-CD9 MoAb to CD9 on the platelet membrane per se induces an increase in the p72syk-associated tyrosine kinase activity but that Fc gamma II receptor-mediated signal(s) is required for the full activation of platelets and the appearance of tyrosine-phosphorylated proteins. The elevated intracellular cAMP level induced by PGI2 acts at a step distal to the activation of p72syk and inhibited the signal transduction pathway leading to protein tyrosine phosphorylation and aggregation. p72syk activation occurs in the absence of aggregation, but aggregation appears to reduce the elevated p72syk activity induced by anti-CD9 MoAb.

Antibodies, Monoclonal↗

PubMed1995

Sulphonylurea agents inhibit platelet aggregation and [Ca2+]i elevation induced by arachidonic acid.

The effects of three hypoglycaemic agents--glimepiride, glibenclamide and gliclazide--were evaluated on platelet aggregation and intracellular Ca2+ elevation induced by arachidonic acid. Platelet aggregation was assessed both by the conventional method using changes in light transmission and by a newly-developed procedure using light scattering which allows the detection of small as well as large aggregates. Glimepiride and glibenclamide inhibited the formation of small and large aggregates induced by optimal concentrations of arachidonic acid in a dose-dependent manner. The ID50 values for the inhibition of platelet aggregation were approximately one third of those for arachidonic acid metabolism, suggesting that both agents have certain direct inhibitory effects on platelet aggregation unrelated to arachidonic acid metabolism. Gliclazide inhibited the formation of small aggregates induced by low concentrations of arachidonic acid to a limited extent. However, it inhibited the formation of large aggregates but not small aggregates when higher concentrations of arachidonic acid were used. Glimepiride and glibenclamide inhibited [Ca2+]i elevation induced by arachidonic acid in a dose-dependent manner, whereas gliclazide had no inhibitory effect. Taken together, these suggest that gliclazide does not inhibit arachidonic acid metabolism but does have certain direct inhibitory effects on platelet aggregation.

Arachidonic Acid↗

PubMed1995

Suppression of azoxymethane-induced colonic aberrant crypt foci by dietary exposure to a novel synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)ethenyl)-2(5H)-furanone, in rats.

The modifying effect of dietary exposure to a novel synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)ethenyl)-2(5H)-furanone (KYN-5) on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. Animals were given weekly s.c. injections of AOM (15 mg/kg body wt.) for 3 weeks to induce ACF. These rats were fed diet containing 100 or 200 ppm KYN-54 for 5 weeks, starting 1 week before the first dosing of AOM. All rats were killed 2 weeks after the last AOM injection, to measure the number of ACF, ornithine decarboxylase (ODC) activity, mucosal polyamine level, and silver-stained nucleolar organizer regions protein (AgNORs) count per nucleus in the colon. In rats given AOM and KYN-54, the frequency of ACF/colon was significantly decreased compared with that in rats given AOM alone. ODC activity and polyamine levels, and the mean AgNORs number in the colon of rats given AOM and KYN-54 at both doses were also significantly lower than that of rats treated with AOM alone. These results provide further evidence that KYN-54 could be a chemopreventive agent against rat colon carcinogenesis.

4-Butyrolactone↗

PubMed1995

Recognition of the structure around the site of cleavage by the carboxyl-terminal processing protease for D1 precursor protein of the photosystem II reaction center.

In order to analyze the structural requirement(s) for proteolytic cleavage, synthetic oligopeptides corresponding to the carboxyl-terminal (COOH-terminal) sequence of the precursor to the D1 protein (pD1) of the photosystem II reaction center, with or without substituted side chain(s) around the cleavage site, were subjected to enzymatic analysis with partially purified processing protease from spinach. The efficiency of action as a competitive inhibitor of the enzymatic cleavage of the COOH-terminal extension, as well as the capacity to serve as a substrate, was used as an indication of effective binding to the protease. Neither a COOH-terminal fragment consisting of the 9 amino acids that are cleaved from pD1 by the protease nor a COOH-terminal fragment of the mature protein consisting of 15 amino acids inhibited the enzymatic processing of pD1. By contrast, a COOH-terminal fragment of pD1 consisting of 24 amino acids, which included the sequences of both the COOH-terminal extension and the COOH-terminal 15 amino acids of the mature protein, was effective both as a competitive inhibitor and as a substrate. This result suggests that the structure formed by linkage between these two parts of the protein moiety is important in the substrate-enzyme interaction. Among substitutions around the cleavage site, the replacement of Leu-343 by Ala (L343A) specifically destroyed the ability of the oligopeptide to serve as either a substrate or an inhibitor, suggesting that the presence of the hydrophobic Leu residue is crucial for the formation of the recognition site. A series of six substitutions at Ala-345 had marked effects on the value of Vmax, without affecting the binding affinity, as represented by Km; the order of substitutions at residue 345 in terms of their effects on Vmax was Ala,Ser,Phe,Cys > Gly > Val >> Pro. With a Pro residue at position 345, the oligopeptide was practically inactive as a substrate.

Amino Acid Sequence↗

PubMed1995

Microsatellite alterations in adenoma and differentiated adenocarcinoma of the stomach.

In order to elucidate the significance of the adenoma-carcinoma sequence in gastric carcinogenesis from a genetic point of view, we examined microsatellite alterations (replication error and loss of heterozygosity) on chromosomes 2p (D2S123), 3p (D3S1317), 5q (D5S409), 9p (IFNA), and 13q (D13S153) as well as p53 gene mutations in 13 adenomas and 23 differentiated adenocarcinomas including 8 early carcinomas of the stomach. Replication error was detected in only one of the adenomas (8%, 1/13) at the D5S409 locus and in none at the other loci, and loss of heterozygosity was also an infrequent event found in one adenoma (14%, 1/7 informative cases) at D5S409 and in none at the other loci. A p53 gene mutation was detected in one (8%, 1/13) of the adenomas. Thus, microsatellite alterations and p53 gene mutations are rare events in adenomas. In differentiated adenocarcinomas, replication error was detected in 4 (17%, 4/23) at single or multiple loci, and loss of heterozygosity was observed frequently at D3S1317 (25%, 3/12), D5S409 (67%, 6/9), and IFNA (26%, 5/19). Mutations in the p53 gene were detected in 9 (39%, 9/23) of the differentiated adenocarcinomas. Microsatellite alterations on several chromosomes and mutations in the p53 gene were frequent in differentiated adenocarcinomas, even those at an early stage. These results suggest that the adenoma-carcinoma sequence is relatively rare in gastric carcinogenesis, and that the majority of differentiated adenocarcinomas of the stomach may develop through a de novo pathway.

Adenocarcinoma↗

PubMed1995

15-cis-beta-carotene found in the reaction center of spinach photosystem II.

Solvent extraction at approximately 4 degrees C in complete darkness, and subsequent analysis by high-pressure liquid chromatography (at approximately 4 degrees C) using an apparatus equipped with a two-dimensional diode-array detector, spectroscopically identified 15-cis-beta-carotene in the reaction center (RC) of spinach photosystem II (PS II). The result revises a previous conclusion that beta-carotene bound to the PS II RC takes the all-trans configuration [Fujiwara, H., Hayashi, H., Tasumi, M., Kanaji, M., Koyama, Y. and Satoh, K. (1987) Chem. Lett. 2005-2008], and generalizes the concept established for purple photosynthetic bacteria that 15-cis-carotenoid is naturally selected by the photosynthetic reaction centers.

Carotenoids↗

PubMed1995

Protein tyrosine phosphorylation in human platelets induced by interaction between glycoprotein Ib and von Willebrand factor.

The interaction between von Willebrand factor (vWF) and glycoprotein Ib (GPIb) induced by ristocetin or botrocetin resulted in associated platelet aggregation, protein tyrosine phosphorylation (PTP) of a 64 kDa protein, as detected by a monoclonal antibody against phosphotyrosine (PY-20), and intracellular Ca2+ elevation that is largely dependent upon Ca2+ influx in human platelets. It is of interest that 75-80, 97 and 125 kDa proteins which are strongly tyrosine-phosphorylated in platelet activation induced by thrombin and other agonists were not detected. Neither vWF nor a coaggregating agent (ristocetin or botrocetin) alone induced aggregation, [Ca2+]i elevation or the 64 kDa PTP. NMC-4, an antibody which inhibits both ristocetin- or botrocetin-induced vWF binding to GPIb, abolished the appearance of the 64 kDa PTP as well as other responses, suggesting that it is specifically induced by the GPIb-vWF interaction. Aspirin, or ONO-3708, a competitive inhibitor of thromboxane A2, did not modify the 64 kDa PTP, while [Ca2+]i elevation was moderately suppressed. Depletion of extracellular Ca2+ or RGD peptides suppressed neither the 64 kDa PTP nor aggregation. H-7, a protein kinase C inhibitor, did not inhibit the 64 kDa PTP, while staurosporine, a potent protein kinase inhibitor, inhibited the 64 kDa PTP and Ca2+ influx, but not aggregation, in a dose-dependent manner. It is suggested that the 64 kDa PTP is associated with platelet aggregation induced by the interaction between GPIb and vWF.

Alkaloids↗

PubMed1995

Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischemic rat hearts.

The aim of the present study was to examine the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on mitochondrial respiration in ischemic rat hearts, and to compare the effects between water-soluble pravastatin and lipid-soluble simvastatin. Either vehicle (0.5% carboxymethyl cellulose), pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Ischemia was induced by ligating the aorta for 60 min in anesthetized open chest rats under artificial respiration. The hearts were removed, mitochondria were isolated, and the respiration was determined by polarography using glutamate and succinate as substrates. When succinate was used as a substrate, the ADP-stimulated respiration (QO3) and ATP production per unit oxygen (ADP/O ratio) were decreased by ischemia. The decreases in QO3 and ADP/O ratio in the pravastatin- and simvastatin-treated groups appeared to be more prominent than those in the vehicle-treated group. This was especially true in the simvastatin-treated group. The ADP-limited respiration (QO4) with succinate in the vehicle-treated heart was slightly increased by ischemia, while that in the pravastatin- or simvastatin-treated hearts was decreased. In conclusion, HMG-CoA reductase inhibitors may result in worsening of myocardial mitochondrial respiration during ischemia.

Adenosine Diphosphate↗

PubMed1995

Activity in the human primary motor cortex related to arm and finger movements.

With the purpose of mapping representations of the finger and proximal arm in the human primary motor cortex (MI), we measured regional cerebral blood flow (rCBF) in eight right-handed normal volunteers during self-paced finger and proximal arm movements. Each movement activated two different fields in MI, one located deep in the anterior lip of the central sulcus and the other relatively close to the surface of the precentral gyrus. Arm fields were located higher than finger fields. A superficial arm field and a deep finger field partially, overlapped. The results indicate that there are two spatially separate motor representations of the finger and proximal arm in the human MI.

Adult↗

PubMed1995

Neurochemical heterogeneity of the primate nucleus accumbens.

In order to further investigate the neurochemical anatomy of the primate nucleus accumbens (NAC), the distributions of the neuropeptides leucine-enkephalin (Leu-ENK), neurotensin (NT), and substance P (SP) and of haloperidol-induced c-fos expression were investigated in the macaque monkey using immunohistochemical methods. To define the boundaries of the NAC, dopamine (DA) and tyrosine hydroxylase (TH) immunohistochemistry was performed. In addition, to formulate the distinction between subdivisions of the nucleus accumbens, immunohistochemistry for calbindin-D28 (CBD) and SP was employed. In general, the medial part of NAC, which consisted of small to medium-sized cells, was low for CBD immunoreactivity and moderate to high for SP immunoreactivities, while the dorsolateral part, which was composed of small cells, showed the opposite pattern of immunostaining for CBD and SP. Many Leu-ENK-immunoreactive perikarya were observed in the dorsal NAC at its middle and caudal levels. There were moderate densities of Leu-ENK-positive fibers throughout the medial part of the NAC. At the dorsolateral margin of the NAC, Leu-ENK-positive fibers formed patches. Most NT-positive perikarya were found in the dorsolateral subdivision. SP-positive perikarya were scarce in the NAC. Dense distribution of NT- and SP-containing fibers or puncta were observed in the mediodorsal part (medial subdivision), where a dense field of DA-immunoreactive fibers was observed. The ventral part (ventral subdivision) contained moderate numbers of NT- and SP-immunoreactive fibers. Haloperidol-induced c-fos expression was very extensive in the medial half of NAC, particularly in the mediodorsal region, which overlapped with the DA- and peptide-rich region. The present study indicates that the NAC of the primate can be subdivided into at least three subterritories, the dorsolateral, medial and ventral subdivision, by neuropeptide histochemistry as well as by the response of its constituent neurons to haloperidol.

Animals↗

PubMed1995

A mirror image of the first and second branchial arch syndrome associated with cleft lip and palate in monozygotic twins.

A rare case of monozygotic twins revealing a mirror image of the first and second branchial arch syndrome with accessory ear and hemifacial microsomia, associated with unilateral cleft lip and palate, is presented. Although the concordance and/or discordance rate of monozygotic or dizygotic twins with cleft lip and palate is well reported, that of twinning of the first and second branchial arch syndrome has been very rarely described. First and second branchial arch syndrome occurs sporadically but cleft lip and palate are strongly related to the influence of environmental factors with a considerable hereditary tendency. The study of twinning of congenital anomalies is important in the investigation of the pathogenesis of genetic and environmental effects. The twins were diagnosed as monozygotic with almost complete certainty by ABO blood typing, HLA typing, finger prints, and DNA typing. Concordance was noticed, which suggests a hereditary tendency. Since concordance in these monozygotic twins was exhibited by a precise mirror image of first and second branchial arch syndrome, spinal scoliosis and cleft lip and palate, it is possible that an environmental factor induced these complex anomalies.

Abnormalities, Multiple↗

PubMed1995

Distribution of nitric oxide synthase in the central nervous system of Macaca fuscata: subcortical regions.

The distribution of nitric oxide synthase-immunoreactive neurons was studied in the Macaca fuscata by immunohistochemistry using antiserum against nitric oxide synthase. In the macaque lower brainstem, many nitric oxide synthase-containing cell bodies were found in the gigantocellular and parvocellular reticular nuclei, the nucleus of the spinal tract of trigeminal nerve, the cochlear nucleus, the prepositus hypoglossi and the nucleus of the solitary tract. Many nitric oxide synthase-immunoreactive perikarya were observed in the laterodorsal-pedunculopontine tegmental nucleus complex of the macaque pontine and midbrain tegmentum. In addition, there were many highly immunoreactive cell bodies in the superficial layers of the inferior and superior colliculi. In the forebrain, numerous cell bodies were observed in the caudate nucleus, putamen, nucleus accumbens, nucleus of the diagonal band, anterior perforated substance and amygdaloid complex. Whereas most of these neurons were labeled highly intense for nitric oxide synthase, there were also many lightly labeled nitric oxide synthase-immunoreactive neurons in the substantia innominata, globus pallidus, ansa peduncularis and lateral hypothalamic nucleus. The present observation indicated some species difference in the distribution of central nitric oxide synthase-containing neurons. Furthermore, the present neuroanatomical evidence that nitric oxide synthase is distributed in a variety of specific neuronal systems, with some differences in the patterns of cytoplasmic localization, further indicates the neural messenger role of nitric oxide in the central nervous system.

Amino Acid Oxidoreductases↗

PubMed1995

Effects of catechins on the mouse tumor cell adhesion to fibronectin.

We studied the effects of 5 kinds of catechins on the adhesion of mouse lung carcinoma 3LL and melanoma B16F10 cells to the fibronectin substratum. (-)-Epicatechin gallate and (-)-epigallocatechin gallate were active in inhibiting the 3LL cell adhesion, while (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin were inactive. Gallate-containing catechins also impaired adhesion and/or spreading of B16F10 cells.

Animals↗

PubMed1995

Effect of fish oil on the development of AOM-induced glutathione S-transferase placental form positive hepatocellular foci in male F344 rats.

Omega-3 fatty acids, which are contained in fish oils and certain vegetable oils in contrast to corn oil or safflower oil rich in omega-6 fatty acids (linoteic acid), have been reported to reduce the carcinogenesis in several organs. In this study, the modifying effect of menhaden fish oil was investigated on the occurrence of azoxymethane (AOM)-induced glutathione S-transferase placental form (GST-P) positive hepatocellular foci, recognized preneoplastic lesions in the liver, in male F344 rats. Starting at five weeks of age, groups of animals were fed ad libitum a semipurified diet containing 5% corn oil (low fat). At seven weeks of age, all animals except the vehicle-treated groups were injected subcutaneously with AOM (15 mg/kg body wt, 1x/wk for 2 wks). Four days after the second injection, groups of animals were fed the diets containing 4% menhaden oil + 1% corn oil (low fish oil diet), 22.5% menhaden oil + 1% corn oil (high fish oil diet), and 5% corn oil. Thirty-four weeks after AOM injections, all animals were necropsied. Livers were sectioned and performed immunohistochemical staining of GST-P for quantitative analysis of enzyme altered foci of the liver. The results demonstrate that the density and the unit area of AOM-induced enzyme altered foci in the liver were significantly lower in the high fish oil group (0.60 +/- 0.08/cm2, 3.0 +/- 0.4 x 10(-4)) than in the 5% corn oil group (2.71 +/- 0.33/cm2, 16.6 +/- 2.6 x 10(-4)) and the low fish oil group (1.66 +/- 0.33/cm2, 11.1 +/- 1.9 x 10(-4)).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Chemoprevention of urinary bladder carcinogenesis by the natural phenolic compound protocatechuic acid in rats.

The modifying effect of dietary administration of protocatechuic acid (PCA) during the initiation and postinitiation phases on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis was investigated in male F344 rats. Animals were divided into nine groups and groups 1-7 were given 0.05% BBN in drinking water for 6 weeks to induce bladder neoplasms. Rats in groups 2, 3 and 4 were fed diets containing 500, 1000 and 2000 p.p.m. PCA respectively for 8 weeks, starting 1 week before BBN exposure. Groups 5, 6 and 7 were fed the PCA-containing diets at three dose levels for 33 weeks. Group 8 was fed the diet containing 2000 p.p.m. PCA alone throughout the study. Group 9 was given tap water without BBN and the basal diet without PCA and served as an untreated control. At 41 weeks after the start, all animals were killed. The incidence of bladder tumors and preneoplastic lesions, and cell proliferation activity estimated by the numbers of silver-stained nucleolar organizer regions proteins (AgNORs) and proliferating cell nuclear antigen (PCNA)-immunoreactive cells were compared among the groups. PCA administration at 1000 and 2000 p.p.m. during the initiation and postinitiation phases significantly decreased the carcinoma incidence in a dose-dependent manner. Also, PCA at all doses given during either initiation or postinitiation phases reduced the development of the preneoplastic lesions. PCA feeding significantly reduced the numbers of AgNORs and PCNA-positive cells in the non-lesional transitional epithelium, preneoplasms, and neoplasms in the urinary bladder of rats treated with BBN. These results indicate that dietary administration of PCA is quite effective in preventing BBN-induced bladder carcinogenesis.

Animals↗