OBJECTIVE3-Bromobenzanthrone (3-BBA), an anthraquinone intermediate dye, is extensively used in textile industry. Since, our prior studies have shown that 3-BBA caused significant depletion of ascorbic acid (AsA) levels, the effect of exogenous supplementation of AsA on the urinary elimination of 3-BBA metabolites was investigated.

METHODGuinea pigs were treated with single oral dose of 3-BBA (50 mg/kg b. wt.) in groundnut oil while another group was treated with single oral dose of 3-BBA (50 mg/kg b. wt.) along with 3 day prior and post oral supplementation of AsA. Control groups were either treated with groundnut oil or AsA alone. Urine from individual animals was collected, extracted and analysed on HPTLC.

RESULTSThe highest elimination of 3-BBA (75 microg) was found to be in 0-24 h urine fraction which decreased to 18 microg and 5 microg in the two subsequent 24 hourly fractions of urine. Exogenous supplementation of AsA increased the total urinary elimination of 3-BBA by almost 77%. A total of 10 fluorescent metabolites excluding the parent compound were eliminated in the urine of guinea pigs treated with 3-BBA. Densitometric scanning of chromatogram showed different peaks at Rf 0.18, 0.22, 0.27, 0.34, 0.40, 0.48, 0.56, 0.66, 0.72, 0.80, and 0.95 which were eliminated and marked as urinary metabolite 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 respectively. AsA not only significantly enhanced the elimination of 3-BBA metabolites but also modified the pattern of metabolites drastically in 0-6 h, 6-24 h and 24-48 h urine fractions.

CONCLUSIONThese results indicate that AsA may be useful in protecting the toxicity of 3-BBA by fascilitating the urinary metabolite(s) excretion of 3-BBA.

Administration, Oral ; Animals ; Antioxidants ; pharmacology ; Ascorbic Acid ; pharmacology ; urine ; Benz(a)Anthracenes ; analysis ; metabolism ; Chromatography, High Pressure Liquid ; Guinea Pigs ; Lipid Peroxidation ; drug effects ; Plant Oils ; metabolism ; Time Factors

Although rodents have previously been used in ecotoxicological studies, they are expensive, time-consuming, and are limited by strict legal restrictions. The present study used a zebrafish (Danio rerio) model and generated data that was useful for extrapolating toxicant effects in this system to that of humans. Here we treated embryos of the naive-type as well as a transiently transfected zebrafish liver cell line carrying a plasmid (phAhREEGFP), for comparing toxicity levels with the well-known aryl hydrocarbon receptor (AhR)-binding toxicants: 3,3',4,4',5-pentachlorobiphenyl (PCB126), 2,3,7,8-tetrachlorodibenzo-p-dioxin, and 3-methylcholanthrene. These toxicants induced a concentration-dependent increase in morphological disruption, indicating toxicity at early life-stages. The transient transgenic zebrafish liver cell line was sensitive enough to these toxicants to express the CYP1A1 regulated enhanced green fluorescent protein. The findings of this study demonstrated that the zebrafish in vivo model might allow for extremely rapid and reproducible toxicological profiling of early life-stage embryo development. We have also shown that the transient transgenic zebrafish liver cell line can be used for research on AhR mechanism studies.
Animals ; Benz(a)Anthracenes/toxicity ; Cell Line ; Green Fluorescent Proteins ; Hepatocytes/cytology/physiology ; Larva/drug effects/growth & development ; Lethal Dose 50 ; Polychlorinated Biphenyls/toxicity ; Tetrachlorodibenzodioxin/toxicity ; Water Pollutants, Chemical/*adverse effects ; Zebrafish/*physiology

No abstract available.
9,10-Dimethyl-1,2-benzanthracene* ; Tocopherols*

The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-kappaB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-kappaB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-kappaB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.
Animals ; Benz(a)Anthracenes/pharmacology ; Caffeic Acids/pharmacology ; Cells, Cultured ; Genistein/pharmacology ; Lipoproteins, LDL/metabolism ; Lysophosphatidylcholines/*pharmacology ; Muscle, Smooth, Vascular/cytology/*drug effects/metabolism ; NF-kappa B/antagonists & inhibitors/metabolism ; Oxidative Stress/drug effects ; Phenylethyl Alcohol/analogs & derivatives/pharmacology ; Plasminogen Activator Inhibitor 1/agonists/genetics/*metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Tissue Plasminogen Activator/*metabolism ; Transcription, Genetic/drug effects ; Up-Regulation/drug effects ; Vitamin E/pharmacology

No abstract available.
9,10-Dimethyl-1,2-benzanthracene* ; Carcinogenesis* ; Hyperbaric Oxygenation* ; Submandibular Gland*

No abstract available.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Breast Neoplasms* ; Breast* ; Estrogens* ; Rats*

No abstract available.
9,10-Dimethyl-1,2-benzanthracene ; Animals ; Rats ; Submandibular Gland

PURPOSE: This study was carried out to investigate the effect of irradiation on the expression of proliferating cell nuclear antigen (PCNA) and apoptosis induction during the carcinogenesis in hamster buccal pouch. MATERIALS AND METHODS: Three months old Syrian golden hamsters were divided into control and 2 experimental groups. Hamsters in control group were left untreated on buccal pouchs. Twenty four hamsters were treated with 0.5% DMBA tri-weekly on the right buccal pouch. Forty eight hamsters were treated with 0.5% DMBA tri-weekly and irradiated with the dose of 5 Gy and 10 Gy at 6, 9, 12, 15 weeks after DMBA application. Resected buccal pouches were sectioned and examined for potential expression pattern of PCNA and apoptosis. RESULTS: The PCNA index was increased with the stages of buccal pouch epithelium carcinogenesis except the hyperplasia stage in control group (p<0.05). The irradiation did not effect on the PCNA index in the dysplasia and the carcinoma in situ stage, but in the hyperplasia stage, the PCNA index was increased with 10 Gy radiation and decreased in the carcinoma stage (p<0.05). The apoptotic index was significantly decreased from the carcinoma in situ stage and the lowest in the carcinoma stage. The apoptotic index was significantly decreased in the hyperplasia and dysplasia stage with the 5 Gy irradiation and significantly increased only in the carcinoma stage with the 10 Gy irradiation (p<0.05). CONCLUSION: The PCNA and apoptotic index were varied according to the irradiation period and dosage in each carcinogenesis stage.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Apoptosis* ; Carcinogenesis* ; Carcinoma in Situ ; Cricetinae* ; Epithelium ; Hyperplasia ; Mesocricetus ; Proliferating Cell Nuclear Antigen* ; Radiation Dosage

PURPOSE: To understand the morphologic and molecular changes in carcinogen-induced breast tissues, DMBA (10-dimethy1-1,2 benzanthracene) was administrated in Sprague- Dawley female rats. MATERIALS AND METHODS: At 50 days of age, all experimental rats were given 20 mg DMBA by gastric intubation. Until the seventh week after DMBA administration, six rats were sacrificed every week, thereafter all tumors found during 20 weeks were removed every week. The morphologic changes were evaluated in routinely processed sections stained with H-E and with anti-smooth muscle actin antibody. Mutation of Ha-ras codons 12 and 61 was examined by ARMS (amplification refractory mutation system) method in frozen tissues. RESULTS: The epithelial cell proliferation of terminal end buds began 2 weeks after DMBA treatment and progressed to the 6th week, resulting in microscopic malignant tumor in one of the 7th weeks rats. The tumors were developed in 43 of 62 rats (69.4%); 8 benign lesions in 4 rats and 72 malignant tumors in 39 rats. Mutations in the 12th and 61th codon of Ha-ras gene were respectively found in 29.7% and 2.7% of preneoplastic breasts, 25% in benign lesions, 2.6% and 31.6% of malignant tumors. CONCLUSION: DMBA treatment in rats induced epithelial proliferation, then benign and malignant tumors through Ha-ras gene mutation, especially in codon 61 leading to cancer.
9,10-Dimethyl-1,2-benzanthracene* ; Actins ; Animals ; Arm ; Breast ; Codon ; Epithelial Cells ; Female ; Genes, ras ; Humans ; Intubation ; Rats*

Cancer chemoprevention can be defined as prevention or intervantion of cancer by the administration of one or chemical entities, either, either as individual drugs or as naturally occurring constituents of the diet. The name capsaicin(trans-8-methyl-N-vanillyl-6-nonenamide) was given by Thresh in 1848, and capsaicin is a primary pungent and irritating princple present in red peppers which are windely used as spices in korean food. The inhibitory effect of capsacin on stomach or skin cancers had been reported in lots of animal studies, but there were few reports In offal cancer carclnogenesls. This study is aimed to see the effect of capsalcln upon DMBA induced cancer of the buccal pouch in hamsters. In thls study, 87 Golden Syrian hamsters, weighing about 80-90g, were used and divided into 5 group : normal group (n=2)-untreated : control group(n=15)-DMBA painted : experimental group I(n=23)-capsaicin(10 micromol/2ml) and DMBA painted ; experimental groupII(n=23)-capsaicin administered and DMBA painted ; experimental group III(n=24)-administered and patinted. DMBA painted. According to groups, the animals were sacrificed at 5, 8, 11, 14, 17 week. Microscopic examination was done and BrdUrd labeling Index was calculated. The results are as follows : 1. According to gross examination, the leukoplakia at 5 week and the papilloma at 8 week were shown in the experimental group I, III. Those feature were appeased rapider than those of the control and expefimental group II. 2. According to gross examination, the exophytic tumorous lesions were shown in the control and all of the experimental groups from 14week, but the features of the control group were severer than those of the experimental groups. 3. According to histopathologic features, the papilloma was shown in all of the experimental group except the control group at 8 week 4. Histologically, the features of the control group were severer than those of the experimental groups from 14 week and there were similar features among the experimental group I, II, III at 17 week 5. At 8 week, BrdUrd labeling index of experimental group I, III were than that of control group and it was statistically significant (p<0.05) 6. The BrdUrd labeling index of experimental group III from 11week, experimental group I from 14week, experimental group II from 17 week were lowed than that of the control group respectively and It was statistically significant(p<0.05) 7. In the distribution of the BrdUrd labeled cells, BrdUrd was more significant in the basal and parabasal cell in dysplatic changes, but in carcinoma in situ, BrdUrd showed a irregular arrangement throughout the whole thickness of the tumor epithelium According to the abone results, the irritating property of the capsaicin accelerated the carcinogenesis in early phase, but the inhibitory effect was shown from carcinoma in situ phase. So the chemopreventive effect of the capaicin which is a major ingredient of red pepper can be expected. However, the further studies including the amount and method of capsaicin administration for preventive effect of oral cancer, should be followed.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Capsaicin* ; Capsicum ; Carcinogenesis ; Carcinoma in Situ ; Chemoprevention ; Cricetinae* ; Diet ; Epithelium ; Leukoplakia ; Mesocricetus ; Mouth Neoplasms ; Paint ; Papilloma ; Skin Neoplasms ; Spices ; Stomach ; Wind