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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
The Korean Society of Toxicology
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Volume 14, Issue 4 - Dec 1998
Volume 14, Issue 3 - Sep 1998
Volume 14, Issue 2 - Jun 1998
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Effects of the ex-vivo Immunotherapy on the Mammary Gland Tumorigenesis Induced by 7, 12-dimethylbenz[a]anthracene(DMBA) in rats
Toxicological Research, volume 14, issue 4, 1998, Pages 465~474
This study was examined on the effect of ex-vivo immunotherapy in 7, 12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Sprague-Dawley female 40 rats were divided into Jour groups. As a positive control, Group I was intubated with DMBA, 5 mg /100 g body weight and single dose, at experimental onset. Group II was treated ex-vivo immunotherapy with polyinosinic-polycytidylic acid (Poly I : C) and Group III was treated with Interleukin-2 (IL-2). Group IV was negative control. All rats were sacrificed at 16 weeks after DMBA intubation. Mammary gland wet weight, dry fat free tissue weight, incidence of tumor, and the number of lobules, alveolar buds, terminal end buds, and terminal ducts were examined. Morphological changes of the mammary gland after treated with DMBA were analyzed by whole mount and histopathological method. As results, the induced mammary tumors of Group I, II and III were 60%, 33% and 0%, respectively. Histopathological types of induced-mammary tumors were adenoma, adenocarcinoma and carcinosarcoma. In analysis of the whole mount method, the number of the terminal end buds, terminal ducts and lobules were significantly lower in Group II (p<0.01) and III (p<0.01) than DMBA alone treated Group I. In microscopic observation, hyperplastic alveolar nodules were significantly lower in Group III than Group I (p<0.01). In conclusion, IL-2 had strong inhibitory effect on the mammary gland tumorigenesis induced by DMBA in rats. Whole mount method may be a useful technique to assess the mammary carcinogenesis. Moreover, hyperplastic alveolar nodules were very sensitive parameter to assess the mammary carcinogenesis.
Effects of the Pilose Antler on the Experimental Hepatocarcino- genesis and the Natural Killer Cell Activity in Rats
Toxicological Research, volume 14, issue 4, 1998, Pages 475~481
This study was performed to investigate the modifying effect of the general (GPA) and the fermented pilose antler (FPA) on experimental hepatocarcinogenesis and Natural Killer cell activity in rats. Specific pathogen free, 5-week male Sprague-Dawley rats were divided into four groups. To induce hepatocarcinogenesis, diethylnitrosamine (DEN, 200 mg/kg, i.p.) was used as a tumor initiator and was given in a single dose at experimental onset. All rats were given a partial hepatectomy (PH) at 3 weeks after experimental onset. Sodium phenobarbital (PB, 0.05% in diet), GPA (0.075% in diet) and FPA (0. 075% in diet) were given from 2 to 8 weeks. Group I of the initiation control group was only given DEN. As initiation-promotion group, Group II was given DEN and then PB. Group III and IV were given DEN-PB-GPA and DEN-PB-FPA, respectively. In hematological analysis, as compared with Group I. the number of white blood cells were significantly increased in the GPA (p<0.01) and the FPA treated group (p<0.05), respectively. Natural killer (NK) cell activity by flow cytometer (FCM) analysis was higher in group of treated with the GPA (35%) than that of the FPA (27.5%), but not significant. Result of the immunohistochemical staining of the glutathione S-transferase placental form (GST-p) indicated that the number of and area of the pre-neoplastic lesions was not significantly changed in Group III and IV compared Group II, respectively. In conclusion, the GPA and the FPA treatment significantly increased the number od WBC in peripheral blood, but the enhancing NK activity and the modifying effect on the experimental hepatocarcinogenesis were not observed.
The Effect of Glucose Deprivation on the Oxygen Deprivation-induced Changes of [[
]-5-hydroxytryptamine Release in Rat Hippocampal Slices
Toxicological Research, volume 14, issue 4, 1998, Pages 483~488
During cerebral ischemia two important factors such as hypoxia and reduction of glucose can act as modulating stressor affecting the release of amine neurotransmitters including 5-hydroxytryptamine (5-HT). This study was performed to investigate the effect of glucose deprivation on the oxygen deprivation-induced changes of [3H]-5-HT release in the rat hippocampal slices. Experimental groups were divided into 4 groups for this study: normoxic/normoglycemic group, oxygen-deprived group, glucose-deprived group, and oxygen/glucose-deprived group. The hippocampus of rat brain was sliced by 400
thickness with manual chopper. After 30 minutes preincubation in the normal buffer, the slices were incubated for 20 min in buffer containing [3H]-5-HT (0.1 M, 74
Ci) for uptake. To measure the release of [3H]-5-HT into the buffer, the incubation medium was drained of and refilled with fresh buffer every ten minutes through a sequence of 14 tubes. Oxygen deprivation by gassing with 95%
and/or glucose deprivation was done in the 6th and 7th tube. The radioactivities in each buffer and the tissue were counted using scintillation counter. The results were expressed as fractional release. When slices were exposed to oxygen-deprived media for 20 min, the diminution followed by the rebound release of [3H]-5-HT was observed during the post-oxygen deprived period. However, glucose deprivation or oxygen/glucose deprivation markedly increased the release of [3H]-5-HT. which was opposite to the pattern observed in oxygen-deprived group. These results suggested that oxygen deprivation itself inhibits [3H]-5-HT release in rat hippocampal slices during oxygen-deprived period, but additional glucose deprivation convert the inhibitory response to increase of [3H]-5-HT release.
Development of Anticancer Agents from Korean Medicinal Plants(Part 10). The Growth-inhibitory Effect of Taraxaci Herba Extract Against Human Skin Melamoma Cells
Toxicological Research, volume 14, issue 4, 1998, Pages 489~494
In the present study, we have evaluated cytotoxic effects of Taraxaci Herba extract on human skin melanoma cells. The light microscopic study showed morphological changes AG-NOR (argyrophylic nucleolar organizer region) by silver chloride stain, and glycoprotein by PAS reaction of the treated cells. Disruptions in cell organelles were determined by SRB assay.
Effects of Toluene Inhalation on The Concentrations of The Brain Monoamines and Metabolites
Toxicological Research, volume 14, issue 4, 1998, Pages 495~500
The effect of acute toluene exposure on behaviour and monoamine concentrations in the various brain regions were investigated in the rat. Toluene was adminstered via inhalation to rats at concentrations of 0, 1000, 10000, 40000 ppm for 20 min. During exposure to toluene, spontaneous locomotor activity was counted. After exposure, animals were sacrificed instantly and brains were separated. Regional concentratons of brain monoamines (norepinephrine, NE; dopamine, DA; 5- hydroxytryptamine, 5-HT) and its metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; homovanillic acid, HVA; 5-hydroxyindole-3-acetic acid, 5-HIAA) were determined. The changes in locomotor activity during toluene exposure depended on the toluene concentration. At 1000 ppm concentration, spontaneous locomotor activity increased initially and thereafter decreased. At higher concentrations (10000 ppm and 40000 ppm), spontaneous locomotor activity decreased and eventually ceased. A regional analysis of VA, NE, 5-HT, VOPAC, HVA, and 5-HIAA indicated a significant decrease in VA concentrations in cerebellum and striatum while NE and 5-HT concentrations were significantly increased in the cerebellum and cortex. 5-HIAA concentrations were significantly increased in all brain regions. DOPAC concentrations were significantly increased in cerebellum and cortex while decreased in striatum. These results especially indicated that metabolic conversion of DA to HVA in striatum was highly increased by toluene inhalation. However, It remains to elucidate between behavioural responses and monoamine changes.
Acute Oral Toxicity of A Novel Combined Antibiotic(Cefatrizine / Clavulanic Acid) in Rats
Kwon, Jong-Won ; Kang, Kyung-Koo ; Hyun Cho ; Baik, Nam-Gi ; Ahn, Byoung-Ok ; Kim, Gye-Won ; Kim, Won-Bae ;
Toxicological Research, volume 14, issue 4, 1998, Pages 501~505
The acute toxicity study of combined antibiotic (Cefatrizine / Clavulanic Acid), a formulation consisting of cafatrizine and clavulanic acid in a ratio of 2 : 1, was evaluated in rats. The antibiotic was orally administered with single dose in dose levels up to 5 g/kg (0, 1.25, 2.5, 5 g/kg). Treatment-related effects were limited to soft stool excretion and caecal dilatation, but histologically no morphological changes could be detected in caecum. In hematology, serum-chemistry parameters and histopathology, no drug-related changes were found. The results of the present study indicate that cefatrizine / clavulanic acid has a low toxic potential and the oral
values exceed 5 g / kg in rats
Cytosolic Calcium Alteration and Cell Injury by Silica in Rat Hepatocytes
Cha, Seok-Ho ; Cha, Shin-Woo ; Ko, Chang-Bo ; Yu, Soung-Roung ; Kim, Hye-Sun ; Paik, Sang-Gi ;
Toxicological Research, volume 14, issue 4, 1998, Pages 507~513
The purpose of this study was to clarify the effect of silica on cytosolic free calcium mobilization and cell injury in primary cultured rat hepatocytes. Cytosolic free calcium concentration ([Ca
]) was measured employing calcium sensitive fluorescent dye, Fura-2 / AM, and cell injury was evaluated by determination of cellular ATP contents. Silica increased [Ca
], in a concentration-dependent manner in hepatocytes (10
M). Silica caused a biphasic increase in [Ca
], which was composed of an initial rapid rise and following sustained phase.
removal from the medium resulted in abolishment of initial and sustained phase of silica (10
], in hepatocytes. The pretreatment with nifedipine (1
M) attenuated silica-induced [Ca
], increases. Silica decreased cellular ATP contents in a dose-dependent manner. This silica-induced cell injury was attenuated by the pretreatment with EGTA (100
M) and nifedipine (1
M). This study suggests that the elevation of [Ca
], caused by silica may be due mainly to influx through a plasma membrane
channel and hepatotoxicity by silica relate with alteration of calcium homeostasis.ium homeostasis.
Detection of Urinary 8-Hydroxyguanine Adduct as Exposure Biomarker for Oxidative Stress
Toxicological Research, volume 14, issue 4, 1998, Pages 515~523
Oxidative stress by reactive oxygen species (ROS) damages cellular DNA, RNA, proteins, lipids and others causing various diseases such as cancer, arthritis, and heart diseases. 8-Hydroxyguanine (8-OHG) is one of the products formed from DNA or RNA damaged by ROS. Since high amounts of 8-OHG can be excreted in urine, it may serve as a potential biomarker indicating the level of oxidative damage to nucleic acids. Residents in industrial area with severe air pollution are expected to be affected by higher level of oxidative stress from pollutants like polyaromatic hydrocarbons (PAHs), etc. Smokers are also expected to be damaged by higher level of oxidative stress from cigarette smoke components like PAHs than non-smokers. To examine if the determination of the urinary concentration of 8-OHG could be used as exposure biomarker for the oxidative stress caused by air-pollutants, this study was performed to determine and compare the urinary concentrations of 8-OHG in smokers and non-smokers, or non-polluted area residents and polluted area residents. Urine samples were collected and purified by a strong cation exchange and cellulose partition column, then analyzed by HPLC with electrochemical detector at 600 ㎷ potential. Concentrations of urinary 8-OHG in non-smokers and smokers of Seoul area college male students were determined as 15.12
9.68 (ng/mg creatinine) and 34.72
11.72 (ng/mg creatinine), respectively, showing significantly higher level of 8-OHG in smokers than in non-smokers. Urine samples of elementary school students were collected from Sokcho area, which is known to be non-polluted, and 3 representative polluted areas; Yocheon industrial area, Ulsan urban and Ulsan industrial area. The concentrations of 8-OHG in these samples were 12.42
8.27 (ng/ mg creatinine, Sokcho), 22.55
9.12 (ng/mg creatinine, Yocheon), 17.41
2.30 (ng/mg creatinine, Ulsan urban), 55.04
39.73 (ng/mg creatinine, Ulsan industrial). Thus, samples from polluted area tend to have higher level of 8-OHG and the levels of Yocheon and Ulsan industrial area were significantly higher than that of Sokcho area. The results indicate that the residents of polluted industrial area or smokers are more severely exposed to oxidative stress probably caused by air pollutants like PAHs. Thus, the determination of urinary 8-OHG concentration could be used as biomarker for the extent of body exposure to oxidative stress caused by various pollutants.
Covalent Interactions of Toluenediisocyanate with DNA and Proteins
Jeong, Yo-Chan ; Park, Misun ; Kim, Dong-Hyun ;
Toxicological Research, volume 14, issue 4, 1998, Pages 525~533
The covalent interactions of toluenediisocyanate (TDI) with macromolecules were investigated both in vitro and in vivo. In vitro incubations of 2,4- and 2,6-TDI with DNA or proteins resulted in dose-dependent formation of TDI-protein and TDI-DNA adducts. TDI-treated DNA was highly resistant to enzymatic digestion and thermal hydrolysis, but was readily hydrolyzed under acidic conditions by releasing its corresponding toluenediamine (TDA), suggesting that TDI caused the crosslinking of DNA. Reaction of TDI with albumin and globin resulted in the formation of several adducts, and some adducts were formed in blood of TDI-treated rats in a dose-dependent fashion. Administration of TDI to rats resulted also in a dose-dependent binding of TDI to hepatic tissue. Levels of TDI-albumin adducts were 10 times higher than those of TDI-globin adducts; the biological half lives of TDI-albumin and TDI-globin adducts were 1.2 and 12.5 days, respectively. Globin adducts were detected up to 28 days after the treatment. Hepatic TDI protein adducts were persistent for a substantial period whereas the levels of hepatic TDI-DNA adduct were decreased rapidly. These results indicate that the isocyanato group of TDI is not readily hydrolyzed under physiological conditions, is transported to other organs, and is bound to DNA and/or proteins without further metabolic activation. As the adducted products degrade in the body, TDA is released and introduced to the liver. TDA may additionally bind to hepatic tissue after metabolic activation. Thus, the toxic effect of TDI exposure is considered to persist during the lifetime of the adducted biological macromolecules.
Serum Cholesterol Lowering Effects of the Phytosterol Derivative (LPSS) in Rats
Toxicological Research, volume 14, issue 4, 1998, Pages 535~539
The present study was designed to investigate the serum cholesterol lowering effect oj the phytosterol derivative (LPSS) on high cholesterol (HC) diet-induced hypercholesterolemia in male weaning Sprague-Dawley (SD) rats. Rats were fed with HC diet containing 1 % cholesterol and 0.5% cholic acid for 1 week. After 1 week, the LPSS oil suspension (0.32 g/kg B. W.) was orally administered to the rats fed with either basal diet or HC diet groups for 7 days. In addition, the LPSS powder (0.14%) mixed with basal diet or HC diet was Jed to the rats for 7 days. Serum total cholesterol and LDL-cholesterol contents were not altered by administration of the LPSS oil suspension with basal diet. However, they were significantly decreased by administration of the LPSS oil suspension with HC diet at day 14. Also, they were significantly decreased by the LPSS powder mixed with basal diet or HC diet at day 9, 11, 14. HDL-cholesterol contents were not altered by the LPSS oil suspension or LPSS powder. These results indicated that the phytosterol derivative(LPSS) might decrease serum total cholesterol and LDL-cholesterol contents in rats.
Comparison with Some Antioxidants on Hydroxyl Radical in Mouse Whole Brain Culture
Lee, Jeong-Chae ; Lim, Kye-Taek ; Lee, Ki-Seoup ; Jung, Hee-young ;
Toxicological Research, volume 14, issue 4, 1998, Pages 541~545
This experiment carried out to compare the protective effects of some antioxidants to hydroxyl radicals in embryonic mouse whole brain tissue culture. The ICR mouse whole brain (13 embryonic day) was cultured in hydroxyl radical system in which radicals were generated by 20 mU / ml glucose oxidase (GO). In this experiment, to make ferrous iron from ferric iron, iron as an accelerator, and ascorbic acid as a reductant were used. For comparison of the protective effects to hydroxyl radicals, antioxidants such as desferrioxamine (DFX), laccase. water or ethanol extracts from Rhus Vemiciflua Stokes (RVS), and
-tocopherol were used, because they relate to metal ion. The results of this experiment showed that all antioxidants protected effectively the cytotoxicity from hydroxyl radicals in the brain cultures. More than 70% of cell viabilities among different antioxidants was at 1 mM DFX, 1.43
water extract, 12.5
ethanol extract and 50
-tocopherol individually, compared with 20 mU/ml GO alone. In comparison to the antioxidative activities of antioxidants, laccase and extracts from RVS showed strong antioxidative effects even at low concentration.
Subchronic Toxicity of a Combined Preparation of Ticlopidine and Giekgo Biloba Extract Orally Administered to Rats for 30 Days
Kim, Sung Y. ; Hye K. Yim ; Mi Y. Yoon ; Kim, Sang K. ; Lee, Ja Y. ; Soo J. Oh ; Kim, Hye S. ; Sung A. Kang ; Kim, Young C. ;
Toxicological Research, volume 14, issue 4, 1998, Pages 547~555
The subchronic toxicity of a combined preparation of ticlopidine and ginkgo biloba extract (EGb 761) mixed in a ratio of 10: 4 was examined in male and female Sprague-Dawley rats. Rats were treated with the test substance at a dose of 52 mg/kg, 156 mg/kg, or 467 mg/kg intragastrically for 30 consecutive days. Control rats were treated with vehicle only. Each group consisted of 10 rats. No death or abnormal clinical signs were observed throughout the administration period. A transient decrease in body weight gain and food intake was observed in the rats treated with the high dose (467 mg/kg), which was recovered to normal in a week. There were no drug-related differences in urinalysis and hematological results. A significant increase in serum total cholesterol and total protein was observed in both sexes of the rats treated with a dose of 467 mg/kg daily, but all the other values obtained in serum chemistry appeared to be within normal range. A dose dependent increase in liver weight was observed in both male and female rats. Relative kidney weight was also increased in the high dose groups. There was no gross pathological finding at terminal sacrifice. Microscopic histopathological examination did not show any lesion in terms of correlation with administration of the test substance. The results suggest that under the conditions employed in this study no observable effect level (NOEL) of the test substance be 52 mg/kg/day.
Kinetic Studies of Parent Compounds and Its Metabolite by Combined Treatment of Allyl Alcohol with Ethanol in vivo
Toxicological Research, volume 14, issue 4, 1998, Pages 557~562
Allyl alcohol is metabolized in the liver through two steps, first to reactive acrolein by alcohol dehydrogenase (ADH), subsequently to acrylic acid by aldehyde dehydrogenase (ALDH). Since ethanol could compete the same enzymes to be metabolized in the liver, we have determined the plasma concentrations of allyl alcohol and ethanol followed by combined treatment. Pretreatment of rats with 2g/kg ethanol followed by ip administration of 40mg/kg allyl alcohol increased the lethality significantly. Determination of in vivo blood concentrations revealed that ethanol pretreatment caused the apparent decrease in allyl alcohol clearance, whereas acetaldehyde level in blood increased significantly by allyl alcohol treatment, as determined by head space GC analysis. Treatment of 4-methylpyrazole, an inhibitor of ADH, delayed allyl alcohol elimination significantly and reduced its lethality. Collectively, these findings suggested that reduction of allyl alcohol clearance in the presence oj ethanol was mediated through ADH competitive inhibition.
The Pharmacokinetic Study of Josamycin in Flounder by Reversed Phase High Performance Liquid Chromatography
Toxicological Research, volume 14, issue 4, 1998, Pages 563~567
This study was conducted to observe the distribution of josamycin, a macrolide antibiotic in flounder. Josamycin was administered orally to the flounder at the dose of 100 mg 1 kg josamycin in flounder. Josamycin in blood and various organs of flounder was analyzed using reversed phase HPLC. In blood kinetics study, Cmax was shown 9.50
at 45 min. after treatment and then decreased slowly up to 8th day. Concentration of josamycin in muscle was 0.47
/g tissue at 11th day of the treatment and 0.41
/g tissue at 7th day for liver. The concentration of josamycin in all the tested organs except gall bladder was decreased as the time passed. On the contrary, josamycin in gall bladder was increased 3.8 times at the day of 5th compared to that of the 1st day aftreatment.
Roles of Matrix Metalloproteinase-2 and -9 on the H-ras-Induced Invasive Phenotype in Human Breast Epithelial Cells and Human Fibrosarcoma Cells
Kim, Mi-Sung ; Won, Ju-Hye ; Aree Moon ;
Toxicological Research, volume 14, issue 4, 1998, Pages 569~575
One of the most frequent dejects in human cancer is the uncontrolled activation of the ms-signaling pathways. Significant evidence has accumulated to directly implicate members of the matrix metalloproteinases (MMPs) in tumor invasion and metastasis formation. We have previously shown that MMP-9 expression was significantly enhanced in the ras-tranfected HT1080 human fibrosarcoma cells at the mRNA level. In the present study, we investigated the roles of MMP-2 and -9 on the H-ras-induced invasive phenotypes of MCF 10A human breast epithelial cells and HT 1080 human fibrosarcoma cells. We show that H-ras is able to induce or enhance a signaling pathway leading to the enhancement of an invasive phenotype in both MCF10A and HT1080 cells as determined by matrigel invasion assay. We then examined the effect of H-ras activation on the expression of MMP-2 and -9 by measuring enzymatic activities and mRNA levels. Our data clearly demonstrated that H-ras prominently induces expression of MMP-2 in MCF10A cells, while it efficiently up regulates MMP-9 in HT1080 cells. Taken together, these findings suggest that the correlation between ras-mediated invasiveness and enhanced expression of MMPs may be cell type-specific: MMP-9 is closely associated with the invasive phenotype induced by ras activation in fibrosarcoma cells, whereas MMP-2 is more likely associated with it in epithelial cells.
Induction of Oxidative Stress and Cytoskeleton Damage by Cadmium in WB-F344 Rat Liver Epithelial Cells
Toxicological Research, volume 14, issue 4, 1998, Pages 577~585
Cadmium is an important industrial and environmental pollutant and has adverse effects on cell growth and metabolism, although the mechanisms of its cellular toxicity are still unclear. This study was performed to elucidate the cytotoxic mechanism of cadmium in the viewpoint of oxidative stress and cytoskeleton alterations in WB-F344 rat liver epithelial cells. 200
caused a severe disassembling of microtubule and micro filament and an apparent cell retraction under an observation with fluorescence micoscope. (equation omitted)-tubulin and F-actin protein were highly thiolated at 20 min and then disappeared from 1 hour after the treatment of 200
in the immunoblot analysis. Intracellular GSH was decreased from 1hr to 24 hrs by 66.6 or 200
. Intracellular protein thiol was also decreased by 22.2, 66.6 and 200
at 1 hour after its treatment. The product of lipid peroxidation (malondialdehyde) was increased from 4 hrs by 66.6 and 200
. These data indicate that cadmium induces oxidative stress involving disassembling of microtubule and micro filament, thiolation of (equation omitted)-tubulin and actin protein, depletion of GSH and protein thiol, and increase of lipid peroxidation.
Comparison Between TCDD and 3MC Action on CYP1A1 Expression and EROD Activity in the Isolated Perfused Female Rat Liver
Ahn, Mee R. ; Sheen, Yhun Y. ;
Toxicological Research, volume 14, issue 4, 1998, Pages 587~594
In order to understand the mechanism if the regulation of CYP 1A1 gene expression and ethoxyresorufin deethylase (EROD) activity in ex vivo system, we have studied the action of TCDD and 3MC in the isolated perfused female rat liver. CYP1A1 mRNA level and EROD activity were measured in rat liver that was isolated and perfused with various chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), 17
), morin. TCDD or 3MC alone perfusion into female rat liver resulted in increase of CYP 1A1 mRNA level and the magnitude of stimulation was six times higher with TCDD treatment than 3MC treatment. However E
perfusion into female rat liver showed inhibition of CYP 1A1 mRNA level. When 10
was administered concomitantly with either 10
M TCDD or 10
M 3MC, stimulated CYP 1A1 mRNA by either TCDD or 3MC was inhibited. Morin was examined for its effects on CYP 1A1 mRNA level and result was similar to that was observed with estrogen. EROD activity was also stimulated with either TCDD or 3MC perfusion, and the magnitude of EROD stiumlation was smaller than that of CYP 1A1 mRNA stimulation in response to TCDD or 3MC perfusion. Unlike CYP1A1 mRNA level, stimulation of EROD activity was greater with 3MC than TCDD. Concomitant perfusion either E
or morin with TCDD or 3MC inhibited 3MC perfusion or TCDD perfusion stimulated EROD activity. These data suggested that TCDD and 3MC might act diffrently in terms of regulation of CYP 1A1 gene expression in rat liver.