Biomedical subjects

K Tamura

Publications and source records attributed to K Tamura.

At least 451 records · Page 25Linked to original sources

PubMed1997

Effect of dietary ascorbic acid on the hepatic microsomal mixed function oxidase system in liver of chicks treated with Escherichia coli lipopolysaccharide.

We determined whether dietary ascorbic acid (0.3 or 3 g/kg diet) modulates hepatic microsomal mixed function oxidase (MFO) system and plasma alpha 1 acid glycoprotein (AGP) concentration in chicks treated with Escherichia coli lipopolysaccharide (LPS). Injection of LPS (250 micrograms/kg body weight every other day) intraperitoneally for 14 days decreased cytochromes P450 and b, content and NADPH-cytochrome c reductase activity in hepatic microsomes in male broilers. Content of cytochromes P450 and b5 was negatively correlated with plasma AGP concentration. Feeding ascorbic acid partly alleviated the reduction of cytochromes P450 and b5 in males. Plasma AGP concentration also increased with the LPS injection and was partly lowered by feeding ascorbic acid. The results indicate that dietary ascorbic acid modulates the responses of the microsomal MFO system and of plasma AGP concentration against repeated injection of LPS in male broiler chicks.

Animals↗

PubMed1997

Plasma angiotensinogen concentrations in obese patients.

A close relationship between obesity and hypertension has been recognized, and plasma angiotensinogen concentrations (p-AGT) have been reported to correlate with blood pressure (BP). However, little is known about AGT in obese patients with hypertension. To define the role of AGT in obese hypertension, we measured p-AGT in obese patients. The subjects were 42 obese patients diagnosed on the basis of a body mass index (BMI) of more than 25 kg/m2, and 21 sex- and age-matched nonobese patients, whose BMI was less than 25 kg/m2. The hypertensive patients had not previously received antihypertensive drugs. P-AGT (P < .05) and mean BP (P < .0001) was increased in the obese patients as compared with the nonobese patients. Positive correlations were observed between BMI and p-AGT, mean BP and p-AGT, and BMI and mean BP (all P < .05). However, after adjustment for blood pressure, p-AGT was not different between groups, and after adjustment a positive correlation remained only between BMI and mean BP. These results suggested the possible involvement of increased p-AGT in hypertension in obese patients, although this may be a secondary change to hypertension or obesity.

Adult↗

PubMed1997

Effect of stereochemistry on the transport of Aca-linked beta-turn peptidomimetics across a human intestinal cell line.

Transcellular transport is one of the most important barriers facing the development of new therapeutic agents. However, little is known about the specific effects of structure and particularly stereochemistry on cell permeability. An attractive in vitro model has been developed for the direct assessment of cell transport, using the immortalized human epithelial cell line, Caco-2. The present study assesses the effects of stereochemistry on transport in a commonly used beta-turn model system. Thus, L,L- and L,D-Ala-Ala were cyclized with aminocaproic acid, resulting in macrocycles in which the dipeptides correspond to the i + 1 and i + 2 positions of a beta-turn. The transport of these dipeptides across a Caco-2 cell monolayer was determined, along with corresponding acyclic models (L,L- and L,D-CH3CH2C(O)-Ala-Ala-n-Pr). The transport studies were carried out in the presence and absence of verapamil, a known inhibitor of the apically polarized efflux system present in Caco-2 cells. Both apical-->basolateral and basolateral-->apical transport were measured. Measurements made in the presence of verapamil showed that the cyclic peptides experienced a ca. 4-5-fold difference in intrinsic flux depending on stereochemistry, with the L,D isomer being transported at a higher rate. These differences disappeared in the acyclic cases examined (permeability coefficient ratios of the L,D/L,L isomers were 1.04-1.13). These observations are discussed in terms of the conformations and hydrogen-bonding characteristics of the compounds as determined by NMR spectroscopy.

Biological Transport↗

PubMed1997

Distribution of alpha 1B-adrenergic receptor mRNA expression along rat nephron segments.

Although several alpha-adrenergic receptor genes are expressed in the rat kidney, little information is available on their expression in the renal nephron segments. We investigated the distribution of alpha 1B-adrenergic receptor mRNA in rat nephron segments using reverse transcription and polymerase chain reaction (RT-PCR). The nephron segments of six- to eight-week-old male Sprague-Dawley rats were microdissected. Total RNA was prepared by the acid-guanidinium-phenol-chloroform method and used in the following RT-PCR assay. The PCR products were size-fractionated with electrophoresis, visualized with ethidium bromide staining and confirmed by Southern blot analysis. Because the PCR primers spanned an intron, the amplification product of the predicted size was considered to be from alpha 1B-adrenergic receptor cDNA and not from genomic DNA. The PCR products were detected in glomerulus (Glm), proximal convoluted and straight tubules (PCT, PST) and cortical and medullary thick ascending limbs of Henle (CTAL, MTAL). No signals were detected in cortical or medullary collecting ducts (CCD, MCD). Large signals were detected in the PCT, and PST, while small signals were found in the Glm, CTAL and MTAL. The alpha 1B-adrenergic receptor mRNA was detected for the first time in rat Glm, PCT, PST and TAL using RT-PCR. alpha 1BAR mRNA seems to be expressed in the specific sites along the nephron and may play significant roles in renal functions, although the specific physiological effects of the renal alpha 1B-adrenergic receptor are unknown.

Animals↗

PubMed1997

Inhibitory effect of a new steroidal saponin, OSW-1, on ovarian functions in rats.

1. This study was undertaken to determine the effects of OSW-1 (3 beta, 16 beta, 17 alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)- (1-->3)-(2-O-acetyl-alpha-L-arabinopyranoside)) on the pituitary-ovarian system and the functions of aortic smooth muscle. 2. A single s.c. injection of OSW-1 (9 micrograms kg-1) on the morning of pro-oestrus inhibited the occurrence of the expected next pro-oestrus, whereas administration of OSW-1 at a dose of 4.5 micrograms kg-1 did not affect the oestrous cycle. OSW-1 treatment on the day of dioestrus-1 did not affect the oestrous cycle. 3. At doses of 4.5 and 9 micrograms kg-1 OSW-1, the serum oestradiol (E2) levels at the expected next pro-oestrus were significantly lower than in control (pro-oestrus). The serum luteinizing hormone (LH) levels 4 days after 9 micrograms kg-1 OSW-1 treatment were also markedly lower than those of control. OSW-1 (4.5 micrograms kg-1) did not affect the levels of inhibin, progesterone and gonadotrophins on the same day. 4. OSW-1 did not inhibit the preovulatory LH surge which occurs on the afternoon of pro-oestrus day. 5. The expression of mRNA coding for the cholesterol side chain cleavage cytochrome P-450 (p450scc), an ovarian steroidal limiting enzyme, was suppressed at 24 and 96 h after OSW-1 treatment. 6. Administration of OSW-1 (9 micrograms kg-1) tended to reduce the relaxation of isolated thoracic aorta ring preparations induced by acetylcholine, while there was no difference in the relaxation induced by sodium nitroprusside. 7. Our results show that OSW-1 inhibits ovarian E2 secretion and that the decrease in E2 secretion may contribute to its effects on the oestrous cycle and the sensitivity of the thoracic aorta to relaxation. The decrease in the levels of ovarian steroids induced by OSW-1 may be due to its direct inhibitory action on the gene expression of the steroidal enzyme and on the proliferation of granulosa cells in the ovary.

Animals↗

PubMed1997

Gianotti-Crosti syndrome associated with cytomegalovirus antigenemia after bone marrow transplantation.

Gianotti-Crosti syndrome (GCS) is characterized by a distinctive self-limiting acral papular or papulovesicular eruption associated with an underlying viral illness. It has not been previously reported in patients post-bone marrow transplantation. We report a 6-year-old Japanese boy who underwent allogeneic bone marrow transplantation from an unrelated donor for acute lymphoblastic leukemia (ALL) in second remission. He had clinical and histopathologic findings characteristic of GCS and evidence of subclinical infection with cytomegalovirus (CMV) detected by CMV antigenemia assay. It is likely that CMV is the causative agent for the GCS in this case.

Acrodermatitis↗

PubMed1997

Ultrastructure of myeloma cells producing parathyroid hormone-related peptide.

We examined the ultrastructure of myeloma cells producing parathyroid hormone-related peptide. The nucleus was mature and the cytoplasm was well-developed, being classified into the mature type with slight nucleo-cytoplasmic asynchrony. Although various nuclear and cytoplasmic abnormalities commonly observed in myeloma cells were recognized, a multilamellar body-like structure which has not been reported previously in myeloma cells was characteristically observed. Numerous nuclear and cytoplasmic abnormalities observed in the myeloma cells of this case were considered to have resulted from increased and aberrant proliferation of myeloma cells. We reported previously that the immature nucleus and various nuclear and cytoplasmic abnormalities are related to poor prognosis. Thus, the ultrastructural findings of myeloma cells in this case is not inconsistent with the short survival time.

Aged↗

PubMed1997

HsMCM6: a new member of the human MCM/P1 family encodes a protein homologous to fission yeast Mis5.

BACKGROUND: The tight regulatory mechanism that prevents more than one round of chromosomal DNA replication per cell cycle is thought to require the function of Mcm/P1 proteins. We report here the structural and functional analyses of HsMcm6, a human homologue of the Mis5 of Schizosaccharomyces pombe. RESULTS: We demonstrate here that the transcription of the HsMCM6 gene was repressed in quiescent cells but was rapidly induced at the G1/S phase by growth factor stimulation. The 5' regulatory region of the HsMCM6 gene was found to harbour four putative E2F binding motifs, and these were responsible for the promoter activity. The HsMcm6 protein level oscillated during the cell cycle, with a peak at the G1/S phase. We also showed that the cell-cycle dependent change of subcellular localization of HsMcm6 resembles those of other Mcm/P1 proteins. HsMcm6 consists of two forms, a form extractable by Nonidet P-40 and the nucleus-bound form. A demonstration of the association of HsMcm6 with HsMcm2 and HsMcm7 in vivo supports the idea that they behave as a heteromeric complex. We mapped the HsMCM6 gene at 2q12-14. CONCLUSION: The results indicate that the behaviour of HsMcm6 is reminiscent of replication licensing factor like other Mcm/P1 family members.

Amino Acid Sequence↗

PubMed1997

Superantigenicity of helper T-cell mitogen (SPM-2) isolated from culture supernatants of Streptococcus pyogenes.

A superantigen (Streptococcus pyogenes mitogen-2; SPM-2) that stimulates human helper T cells bearing unique types of variable domains of T-cell receptor beta-chain (TCR V beta) was isolated from the culture supernatant of S. pyogenes strain T12. The active molecule isolated by diethylaminoethyl (DEAE)-cellulose chromatography and isoelectric focusing was a protein with a molecular weight (MW) of 29,000 and isoelectric point (pl) of 6.0. This new superantigen was found to activate preferentially V beta 4+, 7+, and 8+ T cells, whereas recombinant streptococcal pyrogenic exotoxin A and C activated V beta 12+ and V beta 2+ T cells, respectively, as determined by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) methods. This proliferative response was significantly inhibited by anti-HLA-DR monoclonal antibody, and required paraformaldehyde-fixed antigen-presenting cells (APC), indicating that this action is dependent on major histocompatibility complex (MHC) class II molecules without processing. Analysis of the amino-terminal amino acid sequence of the molecule failed to find any identical or significantly homologous proteins. We have previously reported that cytoplasmic membrane-associated protein (CAP), a streptococcal superantigen isolated from the cell membranes of S. pyogenes T12 strain, stimulated mainly V beta 8+ T cells. Both SPM-2 and CAP preferentially stimulated helper T cells, and rabbit antiserum against SPM-2 completely neutralized the T-cell-stimulating activities of CAP, suggesting that SPM-2 and CAP belong to a family of streptococcal mitogenic proteins. The SPM-2 activity with stimulation of V beta 8+ T cells was detected extensively in the culture fluids of group A streptococci, but not in those of other streptococcal species, including groups B and D streptococci, and most of the activities detected were completely inhibited by anti-SPM-2 serum. These results indicate that SPM-2 may be a newly discovered superantigen molecule, which can be commonly synthesized by group A streptococci.

Amino Acid Sequence↗

PubMed1997

Surgical management of Mycobacterium avium complex disease.

Between July 1991 and October 1996, eight patients with Mycobacterium avium complex (MAC) underwent pulmonary resection in our department. There was equal distribution of men women. The length of the preoperative period averaged 8.1 months (range: 1 to 30 months). Surgical resection was complete, consisting of lobectomy in 4 patients, lobectomy with partial resection in 2, segmentectomy in 1, and segmentectomy with partial resection in 1. There were no major complications postoperatively. No patients had positive sputum culture with MAC just after operation; however, one patient had positive sputum culture 6 months after operation. Our results show the good outcome of resectional surgery for MAC in properly selected patients, who should be operated as early as possible.

Female↗

PubMed1997

Hemodialysis-related arthropathy. A prospective MR study with SE and GRE sequences.

PURPOSE: A prospective examination of hemodialysis-related arthropathy by MR imaging with SE and GRE sequences was undertaken to verify whether the low signal intensity on T2-weighted SE images is caused by a paramagnetic susceptibility effect derived from amyloid or from hemosiderin. MATERIAL AND METHODS: Twenty-seven joints (19 hip joints, 6 discovertebral joints of 5 lumbosacral spines and 1 cervical spine, 2 shoulder joints) in 14 patients undergoing long-term hemodialysis (duration 10-22 years, mean 17) were examined with SE T1-weighted, T2-weighted and GRE T2*-weighted sequences. RESULTS: The signal intensity of the intraarticular and periarticular masses of the involved joints was basically isointense to the muscle in all 3 pulse sequences. No significantly low signal area was found on GRE T2*-weighted images. CONCLUSION: The low signal areas in the hemodialysis-related arthropathy on SE T2-weighted images are not caused by a paramagnetic susceptibility effect, but probably by the hypocellular and fibrous nature of amyloid-containing tissues. Therefore the GRE sequence can be helpful for differentiating hemodialysis-related amyloid arthropathy from chronic hemarthrosis or juxta-articular brown tumor.

Adult↗

PubMed1997

Inhibition by N-(4-hydroxyphenyl)retinamide and all-trans-retinoic acid of exogenous and endogenous development of putative preneoplastic, glutathione S-transferase placental form-positive lesions in the livers of rats.

The effects of N-(4-hydroxyphenyl)retinamide (4-HPR) and all-trans-retinoic acid (tRA) on the exogenous and endogenous models of rat liver carcinogenesis respectively using diethylnitrosamine (DEN) and a choline-deficient, L-amino acid-defined (CDAA) diet were studied. For the exogenous study, male Fischer 344 rats, 6 weeks old, were given a single i.p. dose of 200 mg/kg body wt of DEN, partially hepatectomized at week 3, administered 4-HPR at doses of 0, 0.04, 0.08 and 0.16% or tRA at 0, 0.004, 0.008 and 0.015% in diet from week 2 for 6 weeks, and killed at the end of week 8. For the endogenous study, rats were fed the CDAA diet containing 4-HPR or tRA for 12 weeks and killed at the end of week 12. 4-HPR decreased the numbers and sizes of the glutathione S-transferase placental form-positive foci, assayed as putative preneoplastic lesions, the levels of 8-hydroxyguanine (8-OHG), a parameter of oxidative DNA damage, and the bromodeoxyuridine labeling indices (BrdU L.I.) by all three doses in the DEN-initiated case and, more prominently, in the CDAA diet-associated case. In contrast, while tRA failed to exert inhibitory effects apparently on foci development, 8-OHG formation or BrdU labeling in the DEN-initiated case, it reduced the numbers and sizes of the foci, the 8-OHG levels and the BrdU L.I. by all three doses in the CDAA diet-associated case. Furthermore, both 4-HPR and tRA inhibited the CDAA diet-associated induction of hepatocyte necrosis and connective tissue increase but not intrahepatocellular fat accumulation. These results indicate that 4-HPR exerts chemopreventive effects against the exogenous and endogenous rat liver carcinogenesis, while tRA can inhibit only the latter.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1997

A quinolinone derivative, vesnarinone (OPC-8212), significantly inhibits the in vitro and in vivo growth of human pancreatic cancer cell lines.

A quinolinone derivative, vesnarinone, has been used as a cardiotonic agent. Previous studies have demonstrated that vesnarinone has potent antitumor activity. The present study was designed to assess the antitumor effects of vesnarinone on human pancreatic cancer cell lines in vitro and in vivo. The in vitro effects of vesnarinone on the human pancreatic cancer cell lines (PANC-1, MIA PaCa-2 and BxPC-3) were assessed by the MTT assay, the Trypan blue dye exclusion test and the Matrigel invasion chamber assay. The inhibition of in vivo tumor growth was evaluated on two human pancreatic cancer xenografts (BxPC-3 and SPa-1) transplanted s.c. into nude mice. The dose of vesnarinone for 50% inhibition of cell growth in a 7 day culture ranged between 10 and 20 micrograms/ml as verified by the Trypan blue dye exclusion test. The dose for 50% cytotoxicity after a 3 day culture in the MTT assay was 32 micrograms/ml for PANC-1 and 30 micrograms/ml for BxPC-3, but 50% cytotoxicity for MIA PaCa-2 was not achieved by the maximal dose of vesnarinone (50 micrograms/ml). Nomalsky optic microscopy and acridine orange staining demonstrated the vacuolization and crater-like changes in the cell nucleus after vesnarinone treatment. Moreover, staining of an apoptosis marker (Le(y) protein) and nick end-labeling increased. Vesnarinone also inhibited cancer invasion in the Matrigel invasion chamber assay. In vivo, BxPC-3 and SPa-1 were s.c. transplanted into the nude mice, and vesnarinone (5 or 50 mg/kg) was daily administered orally for 21 days. In both lines, vesnarinone at 50 mg/kg achieved significant inhibition. The present study suggests that vesnarinone may be a new therapeutic agent for pancreatic cancer.

Adenocarcinoma↗

PubMed1997

Fundamental electrophysiologic investigation of spinal cord: refractory period of feline conductive spinal cord evoked potential.

Refractory periods and recovery curves have been used to investigate the physiologic importance and disturbance of peripheral nerves, but the refractory periods of the central nervous system (CNS) have seldom been investigated. We estimated the refractory periods and the recovery curves of the ascending and descending conductive spinal cord evoked potentials (SCEP) in cats. The absolute refractory period of the first and second potentials of both the ascending and descending SCEP was approximately 0.4-0.5 ms. The amplitudes of the first potentials of the ascending and descending SCEP elicited by test stimuli exhibited significant differences, but their latencies did not differ significantly except at the interstimulus interval (ISI) of 1.5 ms, which implies that the same type of fibers was stimulated in the first potentials of the ascending and descending SCEP. The second potential of the descending SCEP elicited by test stimulus showed > 100% amplitude and a maximal recovery of 200% when the ISI was 3.0 ms. The third potential was produced in the test response more easily when a lower vertebral level (L4) was used as the recording site and the ISI was between 1.0 and 4.0 ms. We consider these phenomena to be the result of elimination of the synaptic inhibitory influence by the conditioning stimulus of the paired stimuli for the descending SCEP.

Action Potentials↗

PubMed1997

Pharmacologic profiles of KRH-594, a novel nonpeptide angiotensin II-receptor antagonist.

We studied pharmacologic profiles of KRH-594, dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl-1,3,4 -thiadiazolin-2-ylidene]aminocarbonyl]-1-cyclopentenecarb oxylate, a novel angiotensin II (AII)-receptor antagonist. KRH-594 potently displaced specific binding of [125I]-AII from AT1 receptor with a Ki of 0.39 nM in rat liver membranes, but not from AT2 receptor in bovine cerebellar membranes (Ki > 10 microM). KRH-594 exhibited no affinity for 21 other receptors and two enzymes [50% inhibitory concentration (IC50) > 10 microM], demonstrating its high specificity toward AT1 receptors. In isolated rabbit aorta, KRH-594 caused nonparallel shifts to the right of the dose-response curve to AII and decreased the maximal response with a pK(B) of 10.4. We evaluated the in vivo efficacy and the duration of action in freely moving rats under nonfasting conditions. In normotensive rats, orally administered KRH-594 inhibited AII-induced pressor responses with a 50% inhibitory dose (ID50) of 0.39 mg/kg. In spontaneously hypertensive rats (SHRs), both KRH-594 (1 mg/kg p.o.) and losartan (10 mg/kg p.o.) exerted similar blood pressure-reducing effects, and their effects were still significant at 24 h after drug administration. We concluded that KRH-594 is a specific and efficacious AT1 antagonist that may find its use in the treatment of human hypertension.

Angiotensin II↗

PubMed1997

Effect of aging on B-cell function and replication in rat pancreas after 90% pancreatectomy.

We studied the effect of aging on B-cell function and replication in depancreatized rats. Male Wistar rats, at the ages of 1, 5, and 15 months, underwent 90% pancreatectomy (Px) or a sham operation, and islet function and regeneration were examined 3 weeks later. Plasma glucose levels in 1-month-old rats reached a peak 2 weeks after Px and then declined, while those in 5- and 15-month-old rats reached significant levels as early as the day after Px or 2 days after surgery and continued to increase over the following 3 weeks. Consequently, in contrast to young Px rats, weight loss due to severe diabetes was observed in 5- and 15-month-old Px rats. Plasma glucose responses to intravenous glucose loading (0.5 g/kg body weight) were much greater in older Px rats than in younger rats. There was a marginal insulin response to glucose in 1-month-old Px rats, whereas no insulin response to glucose was observed in older Px animals. The insulin content of the residual pancreas was increased threefold in 1-month-old Px rats, but there was no increase in 5- and 15-month-old Px rats. These data demonstrate that the effect of reducing islet mass is much greater in aged rats than in young rats and that the replicatory capacity of B cells tends to diminish after adulthood has been reached.

Aging↗

PubMed1997

Enhancement of tumor radio-response by irinotecan in human lung tumor xenografts.

We investigated the ability of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11) to increase tumor radio-response in vivo using human lung tumor xenografts. The xenografts were treated with (1) CPT-11 (10 mg/kg) intraperitoneally on days 1, 5 and 9, (2) single dose radiation (10 Gy/leg) on day 1, or (3) a combination regimen of both treatments in which radiation was given 1 h after the first dose of CPT-11. DNA flow cytometry studies were performed to define the cell cycle changes following treatment for 1 to 12 h with 0, 0.5, 2.0 or 8.0 ng/ml SN-38, the major active metabolite of CPT-11. In both small cell lung cancer (MS-1) and small cell/large cell carcinoma (LX-1) xenografts, combination treatment resulted in significant tumor regression compared with the use of CPT-11 (P = 0.0005, 0.0053) or radiation treatment (P = 0.00221, 0.0035) alone. Neither severe body weight loss nor enhanced skin reaction was observed following the combined treatment. In flow cytometry studies, the proportion of cells in G2/M-phase, the most radio-sensitive phase, increased after 1 h exposure to the lowest dose of SN-38 (0.5 ng/ml). These findings suggest that CPT-11 is a potent radiosensitizing agent, and that its activity is related to the cell cycle. This is the first report to indicate that CPT-11 serves as a radiosensitizer in vivo.

Animals↗

PubMed1997

Inhibition by green tea extract of diethylnitrosamine-initiated but not choline-deficient, L-amino acid-defined diet-associated development of putative preneoplastic, glutathione S-transferase placental form-positive lesions in rat liver.

The effects of green tea extract (GTE) on exogenous and endogenous models of rat liver carcinogenesis using diethylnitrosamine (DEN) and a choline-deficient, L-amino acid-defined (CDAA) diet were studied. For the exogenous carcinogenesis study, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal dose of 200 mg/kg body weight of DEN, partially hepatectomized at week 3, and administered GTE at doses of 0, 0.01 and 0.1% in the drinking water from week 2 for 10 weeks. For the endogenous carcinogenesis study, rats were fed the CDAA diet and simultaneously given GTE for 12 weeks. All rats were killed at the end of week 12. After DEN-initiation, the apparent numbers of glutathione S-transferase placental form-positive foci, assayed as putative preneoplastic lesions, were decreased by the administration of GTE, though their sizes were not altered. In contrast, GTE did not significantly reduce the numbers of the lesions induced by the CDAA diet or affect their sizes. While the levels of 8-hydroxyguanine, a parameter of oxidative DNA damage, were reduced by the GTE administration in both experimental models, GTE did not protect against the CDAA-diet-associated liver tissue damage in terms of either histology or plasma marker enzyme levels. We conclude that, while GTE may be a possible chemopreventive agent for nitrosamine-initiated hepatocarcinogenesis in the absence of chronic hepatocyte damage, it does not significantly inhibit lesion development in hepatocarcinogenesis associated with the CDAA diet, a cirrhosis-associated model.

Alanine Transaminase↗