1.Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat.
Ja June JANG ; Kyung Ja CHO ; Yon Sil LEE ; Jong Hee BAE
Journal of Korean Medical Science 1991;6(1):31-36
The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N-methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide-spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis.
Animals
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Capsaicin/pharmacology/*toxicity
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Cocarcinogenesis
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Diethylnitrosamine
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Liver Neoplasms, Experimental/chemically induced/prevention & control
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Lung Neoplasms/chemically induced/prevention & control
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Male
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Methylnitrosourea
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Neoplasms, Experimental/*chemically induced/prevention & control
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Nitrosamines
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Rats
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Rats, Inbred F344
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Urinary Bladder Neoplasms/chemically induced
2.The effect of deferoxamine on the preneoplastic lesions in the chemically induced hepatocarcinogenesis.
Young Nyun PARK ; Woo Hee JUNG ; Chanil PARK
Yonsei Medical Journal 1994;35(4):388-395
Iron is essential for the growth of all living cells. One of the most important intracellular roles of iron is the activation of ribonucleotide reductase, which is indispensible to the production of deoxyribonucleotide necessary for DNA synthesis. Deferoxamine (DFO) is an iron chelating agent and has been known to have an antiproliferative effect in various malignant cells including hepatocellular carcinoma and the effect seems to be related to depletion of iron. This study was undertaken to investigate the effect of DFO on preneoplastic lesions in chemically induced hepatocarcinogenesis. The resistant hepatocyte model was used and Sprague Dawley rats were divided into the following groups; I: normal control, II: carcinogen administered group, III: carcinogen and DFO administered group. Rats were sacrificed at 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks and 8 weeks after partial hepatectomy (PH). DFO (50 mg/kg/day, I.P.) was daily injected from 3 weeks before administration of carcinogen to the time when rats were sacrificed. Hepatic iron content was higher in group II than in group III, especially at 3 days and 1 week after PH. Hyperplastic lesions of resistant hepatocytes were less well developed in group III than in group II. Bromodeoxyuridine labelling indices of oval cells and hyperplastic lesions of resistant hepatocytes were higher in group II than in group III except for rats examined at 3 days after PH. The results suggest that DFO has an antiproliferative effect on preneoplastic lesions in hepatocarcinogenesis and it might be related to reduction of the hepatic iron.
Animal
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Deferoxamine/*pharmacology
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Diethylnitrosamine
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Liver Neoplasms, Experimental/chemically induced/*prevention & control
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Male
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Precancerous Conditions/chemically induced/*prevention & control
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Rats
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Rats, Sprague-Dawley
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Support, Non-U.S. Gov't
3.Chemoprevention of Mammary, Cervix and Nervous system Carcinogenesis in Animals using Cultured Panax ginseng Drugs and Preliminary Clinical Trials in Patients with Precancerous Lesions of the Esophagus and Endometrium.
Vladimir G BESPALOV ; Valeriy A ALEXANDROV ; Andrey Y LIMARENKO ; Boris O VOYTENKOV ; Valeriy B OKULOV ; Mels K KABULOV ; Alexander P PERESUNKO ; Larisa I SLEPYAN ; Viktor V DAVYDOV
Journal of Korean Medical Science 2001;16(Suppl):S42-S53
The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.
Adenocarcinoma/chemically induced/prevention & control
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Adult
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Animal
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Antineoplastic Agents, Phytogenic/*therapeutic use
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Cells, Cultured
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Cervix Neoplasms/chemically induced/prevention & control
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Clinical Trials
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Cytotoxicity Tests, Immunologic
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Disease Models, Animal
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Endometrial Neoplasms/pathology/prevention & control
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Endometrium/pathology
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Esophageal Neoplasms/pathology/prevention & control
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Esophagus/pathology
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Estradiol/blood
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Female
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Fibroadenoma/chemically induced/prevention & control
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Human
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Macrophages, Peritoneal/cytology/immunology
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Male
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Mammary Neoplasms, Experimental/chemically induced/prevention & control
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Mice
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Mice, Inbred C57BL
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Neoplasms, Experimental/chemically induced/*prevention & control
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Nervous System Neoplasms/chemically induced/prevention & control
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Panax/*metabolism
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Precancerous Conditions/pathology/*prevention & control
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Rats
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Tissue Culture
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Uterine Neoplasms/chemically induced/prevention & control
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Vaginal Neoplasms/chemically induced/prevention & control
4.Ethanol extract of Phellinus merrillii protects against diethylnitrosamine- and 2-acetylaminofluorene-induced hepatocarcinogenesis in rats.
Chun-Hung YANG ; Heng-Yuan CHANG ; Yi-Chuan CHEN ; Chia-Chen LU ; Shyh-Shyun HUANG ; Guan-Jhong HUANG ; Hsin-Chih LAI
Chinese journal of integrative medicine 2017;23(2):117-124
OBJECTIVETo study whether the ethanol extract of Phellinus merrillii (EPM) has chemopreventive potential against liver carcinogenesis.
METHODSThirty male Spraque-Dawley rats were randomly divided into control group, EPM control group, hepatocarcinoma control group, low-dose EPM group and high-dose EPM group, 6 in each group. Using the Solt and Farber protocol in a rat model of hepatocarcinogenesis, the chemopreventive effect of EPM on diethylnitrosamine (DEN)-initiated, 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH)-promoted liver carcinogenesis in rats was evaluated. Basic pathophysiological and histological examinations, together with the serum levels of glutamic oxaloacetic transaminase (sGOT), glutamic pyruvic transaminase (sGPT) and gamma-glutamyl transpeptidase (γ-GT) were measured.
RESULTSTreatment of EPM at the concentration of 2 g/kg body weight in the diet for 8 weeks clearly prevented the development of carcinogenesis and reduced the levels of sGOT, sGPT, and serum γ-GT of rats as compared with the hepatocarcinoma control group (P<0.05 or P<0.01). These phenotypes were accompanied by a significant increase in natural killer cell activity.
CONCLUSIONEPM showed a strong liver preventive effect against DEN+2-AAF+PH-induced hepatocarcinogenesis in a rat model.
2-Acetylaminofluorene ; Animals ; Basidiomycota ; chemistry ; Carcinogenesis ; chemically induced ; Cytoprotection ; drug effects ; Diethylnitrosamine ; Ethanol ; chemistry ; Liver Neoplasms, Experimental ; chemically induced ; prevention & control ; Male ; Plant Extracts ; chemistry ; pharmacology ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley
5.The effect of selective cyclooxygenase-2 inhibitor nimesulide on breast cancer induced by dimethylbenzoic acid in rats.
Gui-long GUO ; Xiao-hua ZHANG ; Zhen-xiang YAO
Chinese Journal of Surgery 2005;43(15):1017-1020
OBJECTIVETo study the effect of nimesulide (NIM) on the tumorigenesis of mammary tumors induced by dimethylbenzoic acid (DMBA), and to investigate possible mechanisms of NIM against tumors.
METHODSThe studied rats were randomly divided into four groups: experimental control group, NIM group, diet and drug of NIM control group. The incidence of mammary tumor was observed. RT-PCR, Western blot were used to detect 8 cancerous tissues in every group, randomly. The expressions of cylooxygenase-2 (COX-2) were assessed by immunohistochemistry. The levels of prostaglandin E(2) (PGE(2)) in blood plasma and tumor tissues were determined by means of radio-immunity assay. The apoptosis index and the proliferation index were evaluated by TUNEL assay, immunohistochemical staining for proliferating cell nuclear antigen (PCNA), respectively.
RESULTSThe incidence of mammary tumor was 69.2% in experimental control group, 40.3% in NIM group. There was obviously decreased incidence in NIM group; The expressions of COX-2 mRNA and protein were significantly down-regulated in NIM group compared with experimental control group. The increased levels of PGE(2) synthesis in blood plasma and tumor tissues were significantly decreased by administering NIM (P < 0.05). The apoptosis index was obviously higher, the proliferation index was markedly less in NIM group than experimental control group.
CONCLUSIONSNimesulide could inhibit the tumorigenesis and development of DMBA-induced mammary tumors by inhibition of proliferation and induction of apoptosis. COX-2 and COX-2-mediated PGE(2) synthesis may play an important role in rat DMBA-induced breast cancer.
9,10-Dimethyl-1,2-benzanthracene ; Animals ; Apoptosis ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Dinoprostone ; metabolism ; Female ; Mammary Neoplasms, Experimental ; chemically induced ; metabolism ; prevention & control ; Random Allocation ; Rats ; Rats, Wistar ; Sulfonamides ; pharmacology
6.Chemopreventive effect of celecoxib against DMBA-induced breast cancer and its mechanism.
Hua-feng KANG ; Xi-jing WANG ; Xiao-xu LIU ; Zhi-jun DAI ; Feng-jie XUE ; Xing-huan XUE
Journal of Southern Medical University 2006;26(11):1599-1602
OBJECTIVETo evaluate the chemopreventive effect of celecoxib, a specific cyclooxegenease-2 (COX-2) inhibitor, on chemically induced breast cancer of rats and its effect on COX-2 expression.
METHODS7, 12-dimethylbenz anthracene (DMBA) was administered intragastrically in SD female rats to establish breast cancer models, which were divided subsequently into control group, tamoxifen group and celecoxib group to receive different treatments accordingly. The occurrence rate of breast cancer was observed and the effect of celecoxib on COX-2 and vascular endothelial growth factor (VEGF) expressions assayed by immunohistochemical SP method.
RESULTSThe incidence of breast cancer in tamoxifen group (48.15%) and celecoxib group (50.00%) were both significantly lower than that in the control group (85.71%; P=0.003 and P=0.004, respectively). The positivity rate of COX-2 expression in celecoxib group (28.57%) was significantly lower than those of tamoxifen group (48.15%) and control group (83.33%; P=0.001 and P=0.035, respectively). The positivity rate of VEGF expression in celecoxib group (42.86%) was significantly lower than that of control group (79.17%, P=0.023), but comparable with that in tamoxifen group (46.15%, P=0.863).
CONCLUSIONCelecoxib can significantly suppress DMBA-induced breast cancer in female rats possibly through down-regulation of COX-2 and VEGF expressions.
9,10-Dimethyl-1,2-benzanthracene ; Animals ; Celecoxib ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase Inhibitors ; therapeutic use ; Down-Regulation ; drug effects ; Female ; Immunohistochemistry ; Mammary Neoplasms, Experimental ; chemically induced ; metabolism ; prevention & control ; Pyrazoles ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; therapeutic use ; Tamoxifen ; therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; metabolism
7.Antiproliferative role of Indigofera aspalathoides on 20 methylcholanthrene induced fibrosarcoma in rats.
Sivagnanam Selva KUMAR ; Mudiganti Ram Krishna RAO ; Maruthaiveeran Periyasamy BALASUBRAMANIAN
Asian Pacific Journal of Tropical Biomedicine 2012;2(12):966-974
OBJECTIVETo find out the anticancer effect of Indigofera aspalathoides (I. aspalathoides) on 20-methylcholanthrene induced fibrosarcoma in rats.
METHODSFibrosarcoma was induced in Wistar strain male albino rats by 20-methylcholanthrene. Intraperitoneous (i.p.) administration of 250 mg/kg body weight/day of aqueous extract of I. aspalathoides for 30 d effectively suppressed chemically induced tumors. Parameters such as body weight, liver and kidney weight, tumor weight, mean survival time, behavioral changes, blood glucose, blood glycogen and marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), acid phosphatase (ACP) and 5'-nucleiotidase (5'-NT) in serum, liver and kidney and lipid profiles such as total cholesterol, phospholipids, free fatty acids in liver and kidney of control and experimental animals were studied.
RESULTSFibrosarcoma bearing animals were ferocious and anxious. The mean survival time was found to increase after the treatment. The body weights were significantly decreased (P<0.001) in group II fibrosarcoma animals which steadily increased after the treatment with I. aspalathoides. The liver and kidney weights were significantly increased whereas the tumor weights decreased as compared to the weights in untreated fibrosarcoma bearing rats. The blood glucose and the liver and kidney glycogen levels were found to decrease significantly (P<0.001) in group II animals. Elevated activities of marker enzymes were observed in serum, liver and kidney of fibrosarcoma bearing Group II animals which were normalize after I. aspalathoides treatment. In the liver and kidney of Group II animals the total cholesterol increased whereas the phospholipids and free fatty acid levels decreased (P<0.001) which were normalized after treatment.
CONCLUSIONSThe treatment by I. aspalathoides on fibrosarcoma bearing rats has improved the levels of various parameters indicating its antiproliferative and anticancer activity.
Animals ; Antineoplastic Agents ; pharmacology ; Chemoprevention ; Fibrosarcoma ; drug therapy ; pathology ; Indigofera ; chemistry ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Liver Neoplasms, Experimental ; chemically induced ; pathology ; prevention & control ; Male ; Methylcholanthrene ; Phytotherapy ; methods ; Plant Extracts ; pharmacology ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rats ; Rats, Wistar ; Seeds ; chemistry
8.Dendritic cell vaccine modified by murine mAFP gene enhances immunoprotective effect on liver carcinogenesis and tumor development in mice.
Yu-An XIE ; Zhi-Peng KUANG ; An-Min LIANG ; Xiao-Ling LUO ; Fan YANG ; Ji-Ning WU
Chinese Journal of Oncology 2008;30(4):250-254
OBJECTIVETo construct a dendritic cell vaccine transduced by murine alpha-fetoprotein (mAFP) gene, and evaluate its immunoprotective effect on C57BL/6J mice during the induction of hepatocellular carcinoma by diethylnitrosamines, carbon tetrachloride and ethanol.
METHODSDendritic cells (DCs) were induced and augmented by murine IL-4 and GM-CSF, and transfected by recombinant adenovirus engineered with mAFP gene. Major MHC class I and II, B7.1 (CD80), B7.2 (CD86), CD18a, and CD54 molecules on DC were analyzed by FACS. 80 C57BL/6J male mice were randomly divided into 4 groups (20 mice per group): Simple DC inoculated group, pAdBM5-mAFP-DC inoculated group, pAdBM5-mAFP plasmid inoculated group, and PBS control group. They were immunized once with 5 x 10(5) DCs (0.1 ml)/mouse administered s. c. in the left flank or 100 mg pAdBMS-mAFP plasmid/mouse administered i. m. in the left tibialis anterior muscle. Inoculation was conducted once a week for 4 weeks after 3 times consecutive immunization initially. At the same time of immunization, DEN/CCl4/ethanol were given to induce hepatocellular carcinoma. Tumor incidence was assessed after 20 weeks.
RESULTSA transgenic DC vaccine was successfully constructed and the mAFP transgenic DCs expressed high level molecules of major MHC class I and II , B7.1, B7.2, CD18a, and CD54. After the 20-week induction, the incidence of primary hepatocellular carcinoma (PLC) was 70.0% in simple DC inoculated group, 25.0% in pAdBMS-mAFP-DC inoculated group, 65.0% in pAdBM5-mAFP plasmid inoculated group, and 75.0% in PBS control group. There was a significant difference between group B and other groups (P < 0.05).
CONCLUSIONmAFP transgenic DC tumor vaccine inoculation may induce strong immunoprotection against liver carcinogenesis and tumor development and reduce PLC incidence induced by DEN/CCl4/ethanol.
Adenoviridae ; genetics ; Animals ; B7-1 Antigen ; metabolism ; Cancer Vaccines ; Carbon Tetrachloride ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; metabolism ; Diethylnitrosamine ; Ethanol ; Genetic Vectors ; Histocompatibility Antigens Class I ; metabolism ; Histocompatibility Antigens Class II ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Liver Neoplasms, Experimental ; chemically induced ; immunology ; prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Random Allocation ; Recombinant Proteins ; genetics ; metabolism ; Transfection ; alpha-Fetoproteins ; genetics ; metabolism
9.Anti-mutagenicity activity of dehydroepiandrosterone.
Sun YANG ; Zhaodi FU ; Fang WANG ; Yu CAO ; Rui HAN
Chinese Journal of Oncology 2002;24(2):137-140
OBJECTIVEThe chemopreventive activity and mechanism of dehydroepiandrosterone (DHEA) were studied.
METHODSModel of 7, 12-dimethylbenz (alpha) anthracene (DMBA) induced breast carcinoma in Sprague-Dawley rats, uitra-violet (UV)-induced DNA damage and Salmonella mutation assay were used.
RESULTSIn DMBA-induced rat mammary tumor model, the rats were orally given daily DHEA for 2 weeks before DMBA and continued for 10 weeks after DMBA administration. The results showed significant inhibition of tumor development by DHEA. The incidence of mammary carcinoma also decreased significantly on daily dose of oral 25 mg/kg DHEA with the mean tumor volume per rat also remarkably reduced by 92%. Moreover, 25 mg/kg DHEA treatment could significantly increase the carcinoma latency for about 3.5 weeks as compared with the control. Using polymerase chain reaction (PCR) assay, in vitro 10(-9) mol/L DHEA showed significant inhibitory effect on UV-induced DNA damage by 90%. In Ames test, DHEA was found to decrease DMBA and benzo (alpha) pyrene-induced TA98 and TA100 His(+) revertants markedly and the number of Salmonella clones were significantly reduced by 53.2% and 73.0% on dose of 5 microgram DHEA/plate. It was also shown that in vitro 10(-7) mol/L DHEA could also effectively inhibit the G-6-PDH activity, which might play an important role in its chemoprophylaxis activities.
CONCLUSIONThe results strongly prove that DHEA is a potent cancer chemoprophylaxis agent, which exhibits inhibitory potential on mutation and chemical carcinogen in vivo and in vitro.
9,10-Dimethyl-1,2-benzanthracene ; administration & dosage ; Adjuvants, Immunologic ; pharmacology ; Animals ; Antimutagenic Agents ; pharmacology ; DNA Damage ; drug effects ; Dehydroepiandrosterone ; pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Glucosephosphate Dehydrogenase ; antagonists & inhibitors ; metabolism ; Mammary Neoplasms, Experimental ; chemically induced ; prevention & control ; Mutagenicity Tests ; Rats ; Rats, Sprague-Dawley ; Salmonella ; drug effects ; genetics ; Time Factors ; Tumor Cells, Cultured