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K Okamoto

Publications and source records attributed to K Okamoto.

At least 289 records · Page 16Linked to original sources

Quantitative analysis of the effects of lithium on the reverse tolerance and the c-Fos expression induced by methamphetamine in mice.

To elucidate the mechanism of psychostimulant-induced reverse tolerance [A. Kifune, S. Tadokoro, Modification of stereotype producing and ambulation-increasing effects following repeated administration of methamphetamine in rats, Jpn. J. Psychopharmacol. 11 (1991) 207-214 [11]; N.J. Leith, R. Kuczenski, Chronic amphetamine: tolerance and reverse tolerance reflect different behavioral actions of the dog, Pharmacol. Biochem. Behav. 15 (1981) 399-405 [13]; S. Tadokoro, H. Kuribara, Reverse tolerance to the ambulation-increasing effect of methamphetamine in mice as an animal model of amphetamine-psychosis, Psychopharmacol, Bull. 22 (1986) 757-762 [18]; S. Tadokoro, H. Kuribara, Modification of the behavioral effects of drugs after repeated administration: special reference to the reverse tolerance, Folia Pharmacologica Japonica 95 (1990) 229-238 [19]], the effects of lithium on ambulatory activity [P. Cappeliez, E. Moore, Effects of lithium on an amphetamine animal model of bipolar disorder, Prog. Neuro-Psychopharmacol. Biol. Psychiatry 14 (1990) 347-358 [1]; M. Hirabayashi, M.K. Alam, Enhancing effect of methamphetamine on ambulatory activity produced by repeated administration on mice, Pharmacol. Biochem. Behav. 15 (1981) 925-932 [7]; M. Hirabayashi, S. Okada, S. Tadokoro, Comparison of sensitization to ambulation-increasing effects of cocaine and methamphetamine after repeated administration in mice, J. Pharm. Pharmacol. 43 (1991) 827-830 [8]; T. Miyauchi, K. Kikuchi, S. Satoh, Further studies on the potentiating effect of lithium chloride on methamphetamine-induced stereotypy in mice, Jpn. J. Pharmacol. 31 (1981) 61-68 [14]; H. Ozawa, T. Nozu, H. Aihara, F. Akiyama, M. Sasajima, Pharmacokinetics and general pharmacological actions of lithium salts administered singly or repeatedly, Folia Pharmacologica Japonica 72 (1976) 433-443 [15].] and cerebral c-Fos expression [S. Ceccatelli, M.J. Villar, M. Goldstein, T. Hokfelt, Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress, Proc. Natl. Acad. Sci. USA 86 (1989) 9569-9573 [2]; L. Giovannelli, P.J. Shiromani, G.F. Jirikoski, F.E. Bloom, Expression of c-fos protein by immunohistochemically identified oxytocin neurons in the rat hypothalamus upon osmotic stimulation, Brain Research 588 (1992) 41-48 [4]; B.T. Hope, H.E. Nye, M.B. Kelz, D.W. Self, M.J. Iadarola, Y. Nakabeppu, R.S. Duman, E.J. Nestler, Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments, Neuron 13 (1994) 1235-1244 [10]; T. Miyauchi, K. Kikuchi, S. Satoh, Further studies on the potentiating effect of lithium chloride on methamphetamine-induced stereotypy in mice, Jpn. J. Pharmacol. 31 (1981) 61-68 [14]; F.R. Sharp, S.M. Sager, K. Hicks, D. Lowenstein, K. Hisanaga, c-fos mRNA, Fos, and Fos-related antigen induction by hypertonic saline and stress, J. Neurosci. 11 (1991) 2321-2331 [16].] were investigated in mice injected with methamphetamine (2 mg/kg, s.c., one to five times). The ambulatory activity enhanced by either acute or chronic methamphetamine injection was delayed or diminished by lithium chloride (LiCl) pretreatment [R.G. Fessler, R.D. Sturgeon, S.F. London, H.Y. Meltzer, Effects of lithium on behaviour induced by phencyclidine and amphetamine in rats. Psychopharmacology 78 (1982) 373-376 [3].]. How the Li-sensitive c-Fos expression in the dorsolateral geniculate nucleus and striatum is related to methamphetamine-induced behavioral excitation is unclear. This protocol, in combination with c-Fos expression of mouse cerebral regions, may provide a useful tool for quantitation of ambulatory activity during c-Fos expression.

Animals↗

New marine prostanoids from the okinawan soft coral, clavularia viridis

Two new marine prostanoids-17,18-dehydroclavulone I (1) and clavulolactone I (2)-were isolated from the Okinawan soft coral, Clavularia viridis. Their structures, including absolute configurations, were determined based on the results of spectroscopic analysis and chemical conversions.

Journal Article↗

Total gastrectomy with simultaneous pancreaticosplenectomy or splenectomy in patients with advanced gastric carcinoma.

A splenectomy or distal pancreaticosplenectomy is often performed simultaneously with total gastrectomy in the treatment of gastric carcinoma to facilitate dissection of the lymph nodes around the splenic artery and splenic hilus. However, the negative impact of splenectomy and pancreaticosplenectomy has also been reported. A retrospective analysis was performed to evaluate the outcomes of distal pancreaticosplenectomy and total gastrectomy, splenectomy and total gastrectomy, and gastrectomy alone in the patients with advanced gastric carcinoma without distant metastasis. Prognostic factors were examined. No significant differences existed in 5-year survival in the patients who underwent gastrectomy with splenectomy, gastrectomy with distal pancreaticosplenectomy, or gastrectomy alone. Neither splenectomy, nor distal pancreaticosplenectomy were prognostic factors. However, distal pancreaticosplenectomy was an independent predictor of pancreatic fistula. In conclusion, the addition of distal pancreaticosplenectomy or splenectomy to total gastrectomy for gastric cancer increases the risk of severe complications, but does not improve survival.

Aged↗

Role of N-glycosylation in cathepsin E. A comparative study of cathepsin E with distinct N-linked oligosaccharides and its nonglycosylated mutant.

Cathepsin E (CE), a nonlysosomal, intracellular aspartic proteinase, exists in several molecular forms that are N-glycosylated with high-mannose and/or complex-type oligosaccharides. To investigate the role of N-glycosylation on the catalytic properties and molecular stability of CE, both natural and recombinant enzymes with distinct oligosaccharides were purified from different sources. An N-glycosylation minus mutant, that was constructed by site-directed mutagenesis (by changing asparagine residues to glutamine and aspartic acid residues at positions 73 and 305 in potential N-glycosylation sites of rat CE) and expressed in normal rat kidney cells, was also purified to homogeneity from the cell extracts. The kinetic parameters of the nonglycosylated mutant were found to be essentially equivalent to those of natural enzymes N-glycosylated with either high-mannose or complex-type oligosaccharides. In contrast, the nonglycosylated mutant showed lower pH and thermal stabilities than the glycosylated enzymes. The nonglycosylated mutant exhibited particular sensitivity to conversion to a monomeric form by 2-mercaptoethanol, as compared with those of the glycosylated enzymes. Further, the high-mannose-type enzymes were more sensitive to this agent than the complex-type proteins. A striking difference was found between the high-mannose and complex-type enzymes in terms of activation by ATP at a weakly acidic pH. At pH 5.5, the complex-type enzymes were stabilized by ATP to be restored to the virtual activity, whereas the high-mannose-type enzymes as well as the nonglycosylated mutant were not affected by ATP. These results suggest that N-glycosylation in CE is important for the maintenance of its proper folding upon changes in temperature, pH and redox state, and that the complex-type oligosaccharides contribute to the completion of the tertiary structure to maintain its active conformation in the weakly acidic pH environments.

Adenosine Triphosphate↗

Clinical efficacy of prosthetic mandibular advancement on obstructive sleep apnea syndrome.

In order to clarify the efficacy and indication of prosthetic mandibular advancement (PMA) on obstructive sleep apnea syndrome (OSAS), we made a comparison of both the polysomnographic findings and the upper airway configuration between before and during PMA on 19 OSAS patients. During PMA, there was a significant decreased apnea hypopnea index compared to before treatment. The changes in magnetic resonance imaging of the upper airway during sleep with PMA indicated that the treatment is regarded to be the first choice for OSAS patients with glossopharyngeal obstruction. In addition to that, the treatment might be considered for use in velopharyngeal obstruction.

Airway Resistance↗

Pineal malignant rhabdoid tumor with chondroid formation in an adult.

A pineal tumour in a 27-year-old male is presented with the characteristic histological features of a pineal malignant rhabdoid tumor (MRT) with chondroid formation. Occasionally, tumor cells contained a single well-demarcated hyaline globular inclusion within the cytoplasm adjacent to the nucleus. The stroma of these tumors tends to be densely hyalinized and become chondroid. Immunohistochemical staining was positive for vimentin, epithelial membrane antigen, chromogranin A, synaptophysin, neuron-specific enolase, S-100 protein, and muscle actin. Despite surgery and radiochemotherapy, the tumor recurred in the pineal region and metastasized to the lower lobe of right lung. The patient died 2 years after the initial diagnosis. This is the second published case of central nervous system-MRT appearing in an adult. The clinical and pathological features of pineal MRT in this patient are presented.

Adult↗

The pharmacokinetics of ceftazidime during hemodiafiltration in critically ill patients.

We studied the pharmacokinetics of ceftazidime in 3 critically ill patients undergoing continuous hemodiafiltration (CHDF). Blood samples were obtained from both the arterial and venous sites of the CHDF system 0, 1, 2, 4, 6, and 12 h after the start of ceftazidime administration. Pharmacokinetic variables were calculated by fitting individual concentration-time curves to a two-compartment open model. The elimination phase half-life was 6.86 h, and the total elimination rate constant was 0.17 h(-1). Six hours after the start of administration, the ceftazidime concentration in the arterial site decreased from the peak level of 77.5+/-31.4 (mean+/-standard deviation [SD]) microg/ml to 26.2+/-2.5 microg/ml. The ceftazidime concentration examined in 2 cases decreased to 14.7+/-5.8 microg/ml after 12 h. The results suggested that ceftazidime should be administered at 1 g/day in patients with severe infection during CHDF.

Aged↗

Plate Tectonics at 3.8-3.7 Ga: Field Evidence from the Isua Accretionary Complex, Southern West Greenland.

A 1&rcolon;5000 scale mapping was performed in the Isukasia area of the ca. 3.8-Ga Isua supracrustal belt, southern West Greenland. The mapped area is divided into three units bounded by low-angle thrusts: the Northern, Middle, and Southern Units. The Southern Unit, the best exposed, is composed of 14 subunits (horses) with similar lithostratigraphy, bound by layer-parallel thrusts. Duplex structures are widespread in the Isua belt and vary in scale from a few meters to kilometers. Duplexing proceeded from south to north and is well documented in the relationship between link- and roof-thrusts. The reconstructed lithostratigraphy of each horse reveals a simple pattern, in ascending order, of greenstone with low-K tholeiitic composition with or without pillow lava structures, chert/banded iron-formation, and turbidites. The cherts and underlying low-K tholeiites do not contain continent- or arc-derived material. The lithostratigraphy is quite similar to Phanerozoic "oceanic plate stratigraphy," except for the abundance of mafic material in the turbidites. The evidence of duplex structures and oceanic plate stratigraphy indicates that the Isua supracrustal belt is the oldest accretionary complex in the world. The dominantly mafic turbidite composition suggests that the accretionary complex was formed in an intraoceanic environment comparable to the present-day western Pacific Ocean. The duplex polarity suggests that an older accretionary complex should occur to the south of the Isua complex. Moreover, the presence of seawater (documented by a thick, pillow, lava unit at the bottom of oceanic plate stratigraphy) indicates that the surface temperature was less than ca. 100 degrees C in the Early Archean. The oceanic geotherm for the Early Archean lithosphere as a function of age was calculated based on a model of transient half-space cooling at given parameters of surface and mantle temperatures of 100 degrees and 1450 degrees C, respectively, suggesting that the Archean oceanic lithosphere was rigid. These conclusions-rigidity and lateral plate movement-support the idea that the modern style of plate tectonics was in operation only 0.7-0.8 G.yr. after the formation of the Earth.

Journal Article↗

Redox regulation of the glucocorticoid receptor.

Redox regulation is currently considered as a mode of signal transduction for coordinated regulation of a variety of cellular processes. The transcriptional regulation of gene expression is also influenced by cellular redox state, most possibly through the oxido-reductive modification of transcription factors. The glucocorticoid receptor belongs to a nuclear receptor superfamily and acts as a ligand-dependent transcription factor. We demonstrate that the glucocorticoid receptor function is regulated via redox-dependent mechanisms at multiple levels. Moreover, it is suggested that redox regulation of the receptor function is one of dynamic cellular responses to environmental stimuli and plays an important role in orchestrated crosstalk between central and peripheral stress responses.

Amino Acid Sequence↗

Number and anatomical extent of lymph node metastases in gastric cancer: analysis using intra-lymph node injection of activated carbon particles (CH40).

BACKGROUND: The long-term survival of 200 patients with gastric cancer who underwent radical gastrectomy was analyzed with respect to the number and anatomical extent of lymph node metastasis. All of the patients received intra-lymph node injection of fine activated carbon particle solution (CH40) during surgery. METHODS: The average number of resected lymph nodes increased in line with the anatomical level of lymph node dissection; 32.5 per patient in D1, 42.3 in D2, 3 and 66.3 in D4. The percentage of blackened lymph nodes without metastasis (42.4%) was slightly higher than that of lymph nodes containing metastasis (37.2%), but the difference was not statistically significant. Of the 200 patients, 61 (30.5%) had microscopic evidence of metastatic lymph node involvement. Twenty-two patients had between one and three metastatic lymph nodes, 19 had between four and nine and 20 patients had more than nine. The 5-year survival rate was 93.1% in patients without lymph node metastasis, 71.9% in patients with 1-8 metastatic nodes, 36.1% in patients with 4-9 nodes and 19.2% in patients with > 9 nodes. RESULTS: The 5-year survival rate according to the anatomical extent of metastatic lymph nodes was 93.1% in n0, 63.1% in n1, 37.9% in n2, 27.8% in n3 and 0% in n4. The number of metastatic lymph nodes and also their anatomical extent were identified as independent prognostic factors for survival by multivariate analysis. CONCLUSION: The number and anatomical extent of metastatic lymph nodes have similar impacts on prognosis in gastric cancer.

Adult↗

Trehalose can be used as a parenteral saccharide source in rabbits.

Trehalose is a saccharide that possesses no reducing group and so has possible use in parenteral nutrition, especially because it can be stored with amino acids without undergoing the Maillard reaction. To evaluate this possibility, a series of experiments were conducted. The activity of trehalase, an enzyme that metabolizes trehalose to glucose, was measured in rabbit serum and kidney. Conversion of trehalose to glucose and excretion of trehalose in the urine were measured in rabbits administered 10% trehalose intravenously. The effects on nutritional indices as indicators of its use as an energy source were also measured in rabbits infused with 8.23 g.kg-1.d-1 (4. 12 g.kg-1 on d 1) of trehalose for 5 d. Trehalase activity resembled maltase activity, both being high in the renal cortex (2.04 +/- 0.71 and 2.93 +/- 0.26 micromol.g-1.min-1, respectively), weak in the medulla, and undetectable in the serum. Serum glucose and insulin concentrations were increased significantly by trehalose infusion. Significant elevations were observed in serum glucose but not insulin levels by maltose infusion. On the other hand, urinary excretion of trehalose (1.1 +/- 2.1% of dose) was significantly lower than that of maltose (10.1 +/- 4.9% of dose). Similar effects of trehalose and maltose infusions as seen in normal rabbits occurred in rabbits with alloxan diabetes (urinary excretion rate, 3. 8 +/- 3.0% of the infused trehalose dose and 35.6 +/- 9.7% of the infused maltose dose). Nitrogen balance was positive in the trehalose- and glucose-infused normal rabbits with significant difference from the control group infused with saline, suggesting that trehalose was used as an energy source. These results suggest that trehalose has the potential for use as a saccharide source for parenteral nutrition.

Animal Nutritional Physiological Phenomena↗

Binding analysis of Xenopus laevis translation initiation factor 4E (eIF4E) in initiation complex formation.

A translation initiation factor, eIF4E, of Xenopus laevis was purified by affinity column chromatography after the gene expression as a full-length protein in a baculovirus-insect cell system. Interaction between X. laevis eIF4E and 4E-BP2 was analyzed by affinity column chromatography, gel permeation chromatography (GPC), and surface plasmon resonance (SPR). It was found that the interaction of eIF4E with an mRNA cap-analogue enhanced the binding activity of eIF4E with 4E-BP2. Furthermore, the SPR analysis showed that the eIF4E-cap-analogue interaction was very weak regardless of complex formation of 4E-BP2 with eIF4E; the dissociation constant of eIF4E for the cap-analogue was estimated to be 10(-2)-10(-4) M. These results suggest that the participation of another initiation factor is required for eIF4E to recognize the cap structure in vivo. The results reported in this paper support "the performed complex model" of Lee et al., in which eIF4E binds to the mRNA cap structure after the initiation factors have formed the initiation complex eIF4F.

Amino Acid Sequence↗

Apomodulation as a novel therapeutic concept for the regulation of apoptosis in rheumatoid synoviocytes.

Fas-mediated apoptosis is observed in synoviocytes of patients with rheumatoid arthritis (RA). This process may be involved in the pathophysiology of RA. We have recently found that Fas-mediated apoptosis of RA synoviocytes is associated with activation of two signaling pathways, the c-Jun amino-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and the FADD (Fas-associated death domain protein)/Caspase-8/Caspase-3/PARP (poly(ADP-ribose)polymerase) pathway. The latter appears to be one of the major signaling pathways required for Fas-mediated apoptosis in RA synoviocytes. Interestingly, Fas-mediated apoptosis in synoviocytes may be induced at least in part by tumor necrosis factor-alpha. Paradoxically, tumor necrosis factor-alpha also causes proliferation of synoviocytes. Employing these molecular processes in the treatment of RA, we have recently shown that ex vivo gene transfer of human Fas ligand (hFasL) induced apoptosis of synoviocytes and infiltrated mononuclear cells of RA synovial tissue through cell-to-cell interaction via the Fas/FasL system. We believe that further understanding of the complex regulatory mechanisms of apoptosis in RA synoviocytes would uncover further aspects of the pathophysiologic mechanisms of RA and contribute to the development of new and effective therapies for RA.

Apoptosis↗

Evaluation of oxygen consumption and resting energy expenditure in critically ill patients with systemic inflammatory response syndrome.

OBJECTIVE: To determine whether oxygen consumption VO2), CO2 production, and resting energy expenditure (REE) in critically ill patients differ in varying grades of systemic inflammatory response syndrome (SIRS). DESIGN: Prospective, clinical study. SETTING: Intensive care unit at a university hospital. PATIENTS: Twenty-six critically ill patients requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 100 metabolic measurements were performed. The grade of SIRS and the Acute Physiology and Chronic Health Evaluation II score were evaluated at the time of the metabolic cart study. VO2 and REE differed among the groups inadequate for SIRS (non-SIRS), with SIRS without infection (nonseptic SIRS), and with SIRS with infection (septic SIRS) (125 +/- 37 mL/min/m2 and 855 +/- 204 kcal/day/m2, 135 +/- 33 mL/min/m2 and 948 +/- 214 kcal/day/m2, and 166 +/- 55 mL/min/m2 and 1149 +/- 339 kcal/day/m2, respectively; p < .005). Patients with septic SIRS had higher VO2 and REE than patients with non-SIRS and nonseptic SIRS. CONCLUSION: VO2 and REE differ among groups of patients with non-SIRS, nonseptic SIRS, and septic SIRS. Patients with septic SIRS have higher VO2 and REE than patients with non-SIRS or nonseptic SIRS. The present study shows that classifying patients into three grades (non-SIRS, nonseptic SIRS, and septic SIRS) is a valid predictor of metabolic stress in critically ill patients.

APACHE↗

Susceptibility of TT virus to interferon therapy.

TT virus (TTV) is a newly identified single-stranded DNA virus. We retrospectively analysed serum samples from sixteen patients, infected with both hepatitis C virus (HCV) and TTV, and who had been treated with interferon. An elevated serum alanine aminotransferase level after interferon was associated with persistence of HCV (abnormal in five of seven patients with persistence of HCV compared with normal in all nine patients who showed eradication of HCV) irrespective of persistence of TTV. Comparison of partial viral DNA nucleotide sequences and phylogenetic analysis showed that viral strains that had a high identity to the prototype virus were more resistant to interferon than those showing low nucleotide sequence identity. Although we observed no liver cell injury caused by persistent TTV infection, the mechanism(s) of TTV resistance to interferon should be further investigated for a better understanding of viral diseases and establishment of therapy.

Alanine Transaminase↗

Secretion of hemolysin of Aeromonas sobria as protoxin and contribution of the propeptide region removed from the protoxin to the proteolytic stability of the toxin.

The sequence at the amino terminus region of the hemolysin ofAeromonas sobria is homologous with that of aerolysin of A. hydrophila. However, there is no homology between the two toxins in the sequence at the carboxy terminal region. It has been shown that aerolysin is secreted into culture supernatant as a protoxin. This proaerolysin is activated by the proteolytic removal of a carboxy terminal peptide. However, the role of the carboxy terminal region, which is removed in the activation process, has not been elucidated. In this study, we showed that hemolysin is also secreted as a protoxin into culture supernatant and that prohemolysin is cleaved by the protease of A. sobria between Ser-446 and Ala-447, resulting in the removal of a 42 amino acid peptide. The removal of the peptide converts the prohemolysin into active hemolysin. Subsequently, we mutated the hemolysin gene to delete the last several amino acid residues and expressed the genes in Escherichia coli, in order to examine the role of the carboxy terminal region of prohemolysin. The amounts of these mutant hemolysins accumulated in the periplasmic space of E. coli were very low compared with that of the wild-type. This observation indicated that the carboxy terminal region of prohemolysin contributes to the proteolytic stability of the toxin.

Aeromonas↗

Molecular cloning and characterization of the oprQ gene coding for outer membrane protein OprE3 of Pseudomonas aeruginosa.

We cloned and characterized the oprQ gene coding for outer membrane protein OprE3 of Pseudomonas aeruginosa PAO1. The oprQ gene was composed of 1,275 base pairs including a sequence encoding for the signal sequence and a mature protein with a Mr of 44,602. Computer-aided alignment and hydropathy analyses of the predicted amino acid sequences suggested that OprE3 is a transmembrane protein homologous to outer membrane proteins of P. aeruginosa such as OprD2 (OprD) porin and OprE1 (OprE) porin. Susceptibility to several antibiotics of the strains lacking or overproducing OprE3 was indistinguishable from that of the wild-type strain, suggesting that OprE3 is unlikely involved in the diffusion of carbapenems and other beta-lactam antibiotics.

Amino Acid Sequence↗

Modulating effects of diets high in omega-3 and omega-6 fatty acids in initiation and postinitiation stages of diethylnitrosamine-induced hepatocarcinogenesis in rats.

The effects of sardine fish oil or corn oil on diethylnitrosamine (DEN)-induced hepatocarcinogenesis were investigated in male F344 rats. Starting at 5 weeks of age, animals were divided into 11 groups and fed 23.5% corn oil (HCO) (groups 1 and 7) or 5% corn oil (LCO) (groups 2 and 8), 22.5% sardine oil + 1% corn oil (FO) semipurified diet (groups 3 and 9) or basal diet (CE-2) (groups 4-6, 10 and 11). At 6 weeks of age, all animals except the vehicle-treated groups were given DEN (200 mg/kg body weight, i.p. once weekly for 3 weeks). One week after the final exposure to DEN, groups 1-3 were changed to the basal diet, and groups 4-6 were switched to the HCO, LCO or FO diet, respectively. Animals in groups 1-3 and 10 were given drinking water containing 0.05% phenobarbital (PB). Liver sections from the animals at the termination of the experiment (24 weeks) were doubly stained for glutathione S-transferase placental form (GST-P) and silver-stained nucleolar organizer regions (AgNORs). The multiplicity of hepatocellular neoplasms of group 1 was significantly larger than that of group 2 or 3. The number of GST-P-positive foci of group 2 or 3 was significantly smaller than that of group 1. Among the groups fed the experimental diets in the postinitiation phase (groups 4-6), no significant difference was found in the incidence of liver tumors. AgNORs values of the enzyme-altered foci in rats of the HCO diet groups were larger than those of the other diet groups. These results indicate that the enhancing effect of a high dose of corn oil in hepatocarcinogenesis is mainly present during the initiation phase but not during postinitiation phase, and fish oil rich in polyunsaturated omega-3 fatty acids could inhibit DEN-induced hepatocarcinogenesis in rats.

Animals↗