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Showing papers on "7,12-Dimethylbenz[a]anthracene published in 2005"


Journal ArticleDOI
TL;DR: Obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis.
Abstract: High body mass index has been associated with increased risk for various cancers, including breast cancer. Here we describe studies using 7,12-dimethylbenz(a)anthracene (DMBA) to investigate the role of obesity in DMBA-induced mammary tumor susceptibility in the female Zucker rat (fa/fa), which is the most widely used rat model of genetic obesity. Fifty-day-old female obese (n = 25) and lean (n = 28) Zucker rats were orally gavaged with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors. Rats were killed 139 days after DMBA treatment. The first mammary tumor was detected in the obese group at 49 days after DMBA treatment, as compared with 86 days in the lean group (P < 0.001). The median tumor-free time was significantly lower in the obese group (P < 0.001). Using the days after DMBA treatment at which 25% of the rats had developed mammary tumors as the marker of tumor latency, the obese group had a significantly shorter latency period (66 days) than did the lean group (118 days). At the end of the study, obese rats had developed a significantly (P < 0.001) greater mammary tumor incidence (68% versus 32%) compared with the lean group. The tumor histology of the mammary tumors revealed that obesity was associated with a significant (P < 0.05) increase in the number of rats with at least one invasive ductal and lobular carcinoma compared with lean rats. Our results indicate that obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis.

79 citations


Journal ArticleDOI
TL;DR: CYP1B1 appears to be critical for the immunosuppression of DMBA in mice, suggesting a role for bioreactive metabolites in the spleen cell immunotoxicity produced by DMBA.

72 citations


Journal ArticleDOI
TL;DR: Oral administration of ethanolic extract of J. grandiflorum flowers (JgEt) at a dose of 300 mg/kg body weight for 14 weeks to DMBA‐injected animals completely prevented the formation of tumors in the pre‐initiation period and exerted significant anti‐lipid peroxidative effect.
Abstract: The aim of this study was to investigate the chemopreventive efficacy and anti-lipid peroxidative potential of Jasminum grandiflorum Linn. on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinogenesis. Mammary tumors were developed by a single subcutaneous injection of 25 mg DMBA in 1 mL emulsion of sunflower oil and physiological saline. The tumor incidence and tumor volume that formed in the breast were determined. Oral administration of ethanolic extract of J. grandiflorum flowers (JgEt) at a dose of 300 mg/kg body weight for 14 weeks to DMBA-injected animals completely prevented the formation of tumors in the pre-initiation period. JgEt also exerted significant anti-lipid peroxidative effect and improved the antioxidant defense system in DMBA-treated rats. The results of this study clearly indicate that JgEt has potent chemopreventive efficacy in experimental mammary carcinogenesis and further studies are warranted to isolate and characterize the bioactive principle from JgEt.

39 citations


Journal ArticleDOI
TL;DR: The DMBA suture model in rats yields epithelial derived tumors histologically similar to humans and should prove suitable for the testing of preventive or therapeutic agents.
Abstract: Human ovarian cancer is predominantly of epithelial cell origin (>90% of malignant tumors) and most often presents at an advanced stage with poor prognosis. Most animal models of ovarian carcinoma yield thecal/granulosa cell tumors, rather than adenocarcinomas. Induction of adenocarcinoma in 10-45% of rats following an ovarian implantation of 7,12-dimethylbenz[a]anthracene (DMBA) coated silk suture has been reported. Here, DMBA of 99% purity was melted at 124 degrees C to impregnate a 1 cm length of sterile suture for direct ovarian implantation in Wistar Furth rats at 7 weeks of age. DMBA-treated ovaries showed a nearly complete loss of primary follicles and degeneration of granulosa cells at 16 weeks, consistent with the known toxic response of the ovary to direct DMBA application. No tumors were present. Untreated right ovaries and sham dimethyl sulfoxide-treated ovaries were normal. Ovarian tumors in DMBA-treated rats were first noted at 26 weeks post implantation reaching a cumulative tumor incidence of 77% (23/30) at 52 weeks. Controls showed no evidence of tumor at 52 weeks (0/31). Tumor histology was distributed as well differentiated adenocarcinoma (1/23), poorly differentiated adenocarcinoma (8/23), thecal/granulosa cell tumor (8/23), undifferentiated sarcoma (5/23) and one undifferentiated carcinoma with no adeno character. Tumors occasionally seeded to peritoneal mesentery, spleen and abdominal wall. Adenocarcinomas appeared to originate from the ovarian surface epithelium, with focal papillary extension into cystic space. Epithelial derived tumor cells positively react with antibodies to cytokeratin (8/8), epithelial cell adhesion molecule (Ep-CAM 5/5) and prostaglandin synthetase-1 (COX-1 4/4). Vimentin positive epithelial cells when present in adenocarcinomas (4/7), showed perinuclear staining, quite distinct from the uniformly stained stromal cells in thecal/granulosa cell tumors (8/8). The thecal/granulosa cell tumors were Ep-CAM negative (0/5) and weakly COX-1 positive (4/4). Thus, the DMBA suture model in rats yields epithelial derived tumors histologically similar to humans and should prove suitable for the testing of preventive or therapeutic agents.

36 citations


Journal ArticleDOI
TL;DR: It is indicated that atrazine has a potential for enhancing the growth of mammary tumors, partly through increasing cell proliferation in the promotion/progression stage in female rats under ovarian hormone‐free conditions.
Abstract: Atrazine, one of the most commonly used herbicides in the world, has been reported to have endocrine disrupting effects in vivo. In the present experiment, influence of dietary atrazine on the late promotion/progression stage of mammary carcinogenesis in ovariectomized female Sprague-Dawley rats was examined after a single intragastric administration of 7,12-dimethylbenz(a)anthracene (DMBA). When the incidence of palpable mammary tumors reached about 50%, the animals were subjected to ovariectomy and divided into tumor bearing [DMBA-Tumor(+)] and non-tumor bearing [DMBA-Tumor(-)] groups, with subgroups of each fed a soybean-free diet containing 0, 5, 50, or 500 p.p.m. atrazine for 34 weeks. At the completion of the study, the tumor volume in the 50 and 500 p.p.m. treatment Tumor(+) subgroups was greater than in the 0 p.p.m. control case. In the DMBA-Tumor(-) group, higher incidences and volumes of the mammary tumors, with or without statistical significance (P <0.05), were observed in the 50 and 500 p.p.m. subgroups. Atrazine treatment tended to increase proportion of estrogen receptor alpha-positive tumors and stimulated cell proliferation in the DMBA-Tumor(+) group, but with no clear effects on serum hormone levels. The present study indicates that atrazine has a potential for enhancing the growth of mammary tumors, partly through increasing cell proliferation in the promotion/progression stage in female rats under ovarian hormone-free conditions.

36 citations


Journal ArticleDOI
TL;DR: CDNA microarray analysis was used to elucidate the effects of the green tea polyphenol epigallocatechin-3 gallate (EGCG) on the gene expression profile in a DMBA-transformed breast cancer cell line and documented EGCG-altered expression of genes involved in nuclear and cytoplasmic transport, transformation, redox signaling, response to hypoxia, and PAHs.
Abstract: Since the 1980s, the incidence of late-onset breast cancer has been increasing in the United States. Known risk factors, such as genetic modifications, have been estimated to account for ∼5 to 10% of breast cancer cases, and these tend to be early onset. Thus, exposure to and bioaccumulation of ubiquitous environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs), have been proposed to play a role in this increased incidence. Treatment of female Sprague-Dawley rats with a single dose of the PAH 7,12-dimethylbenz[a]anthracene (DMBA) induces mammary tumors in ∼90 to 95% of test animals. We showed previously that female rats treated with DMBA and given green tea as drinking fluid displayed significantly decreased mammary tumor burden and invasiveness and a significantly increased latency to first tumor. Here we used cDNA microarray analysis to elucidate the effects of the green tea polyphenol epigallocatechin-3 gallate (EGCG) on the gene expression profile in a DMBA-transformed breast cancer cell line. RNA was isolated, in quadruplicate, from D3-1 cells treated with 60 μg/mL EGCG for 2, 7, or 24 h and subjected to analysis. Semiquantitative RT-PCR and Northern blot analyses confirmed the changes in the expression of 12 representative genes seen in the microarray experiments. Overall, our results documented EGCG-altered expression of genes involved in nuclear and cytoplasmic transport, transformation, redox signaling, response to hypoxia, and PAHs.

29 citations


Journal ArticleDOI
TL;DR: Black tea extract provides protection against oxidative damage induced by xenobiotics, and a dose-dependent protective effect of BTE against DMBA-induced depletion in enzymes activity was observed in all three tissues examined.
Abstract: Oxygen free radicals and related reactive species have been implicated in the etiology of many diseases, such as atherosclerosis, neurodegenerative disorders, and cancer. Antioxidant enzymes exist in cells to protect against the effects of these free radicals and other oxygen-derived species, which are produced during the oxidative stress. Tea (Camellia sinensis) is the most commonly consumed beverage worldwide. Both green and black tea are known to possess many pharmacological properties, including antioxidant, antipyretic, antibacterial, and antineoplastic effects. In the present study, the preventive effects of black tea extract (BTE) was evaluated in Swiss albino mice against 7,12-dimethyl benz(a)anthracene (DMBA)-induced oxidative stress. The animals were given 0.5%, 1%, and 1.5% BTE as the sole source of drinking solution for 1 week prior to the administration of DMBA, which was given orally as a single dose of 50 mg/kg body weight. At the end of the study period, the liver, kidney, and prostate tissues were dissected out for the determination of antioxidant enzyme levels (catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase), and lipid peroxidation. A dose-dependent protective effect of BTE against DMBA-induced depletion in enzymes activity was observed in all three tissues examined. Similarly, a significant dose-dependent inhibition of the lipid peroxidation caused by DMBA was observed in the BTE-administered animals in all three tissues examined. Our results revealed that BTE provides protection against oxidative damage induced by xenobiotics.

23 citations


Journal ArticleDOI
TL;DR: The results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism ofDMBA.
Abstract: DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.

20 citations


Journal ArticleDOI
TL;DR: Initial studies indicate that DDT and DMBA can induce cellular and chromosomal alterations in the rat mammary gland, which is consistent with the hypothesis that these agents can induce early events in mammary carcinogenesis.
Abstract: The environmental estrogen, dichlorodiphenyltrichloroethane (DDT), and its metabolites have been implicated in the development of breast cancer through mechanisms that remain to be elucidated. It has been hypothesized that exposure to DDT and its metabolites, during critical periods of development, can contribute to an elevated risk for breast cancer in adults. In the present study, we have investigated the effect of o,p 0 -DDT on mammary gland cell proliferation and chromosomal alterations, in a rat mammary cancer model (commonly used to study human cancer), to gain insights into its potential role in the development of breast cancer. Twentyone-day-old female Sprague-Dawley (SD) rats were administered o,p 0 -DDT, 7,12-dimethylbenz[a]anthracene (DMBA), genistein, DDTþDMBA, or DDTþDMBAþgenistein, over a 14-day period. To determine changes in chromosome number and structure, we used the micronucleus assay as well as multicolor fluorescence in situ hybridization (FISH) region-specific DNA probes for rat chromosomes 4 and 19. Cell proliferation was evaluated using 5-bromo-2 0 -deoxyuridine (BrdU). Significant increases in BrdU-incorporated cells were seen in the rats treated with DDTþDMBA. Although micronucleus frequencies were somewhat elevated in several of the treatment groups, significant increases were not seen in any of them. Significant increases in numerical chromosomal aberrations were detected in all of the DDT- and DMBA-treated groups. Genistein significantly reduced BrdU incorporation and polyploidy in the DDTþDMBA-treated rats. These initial studies indicate that DDT and DMBA can induce cellular and chromosomal alterations in the rat mammary gland, which is consistent with the hypothesis that these agents can induce early events in mammary carcinogenesis. Environ. Mol. Mutagen. 46:43–52, 2005. V C 2005 Wiley-Liss, Inc.

20 citations


Journal ArticleDOI
TL;DR: Se appears to be effective in preventing some of the adverse effects associated with DMBA, as seen in rats treated with this drug.
Abstract: 7,12-Dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention On the other hand, selenium (Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification In this study, rats were administered a single, oral dose of DMBA (12 mg) In the Se group, rats received 20 µg Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA–Se-treated group Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the D

18 citations


Journal ArticleDOI
TL;DR: The results indicate that the MNU model is suitable for detection of modifiers of AA actions, and increases the incidence and multiplicity of mammary tumors were increased at the high dose, but not DMBA+DHPN-treated rats.

Journal ArticleDOI
TL;DR: This study indicates that the enhancement of DMBA-induced mammary carcinogenicity in a relatively low PCB126 dose group might partially involve the higher expression of CYP1B1 and AhR in these carcinomas.

Journal ArticleDOI
TL;DR: The beta-NF-induced increase in the hepatic UDP-GT activity and decrease in the mammary DNA-DMBA adducts occurred under the same treatment regimen that led to suppression of DMBA-induced mammary carcinogenesis.

Journal ArticleDOI
TL;DR: It is indicated that diet modulates DMBA-induced adrenal toxicity in female rats, with increased apoptosis early and reduced necrosis later in rats fed a soy-containing diet.

Journal ArticleDOI
TL;DR: The results indicate that a high incidence of dysplasia was associated with E2 feeding with or without DMBA treatment in the OVX rats, whereas the incidence was low in rats fed DZ or GE and treated with DMBA, suggesting a weak estrogen receptor agonist of Dz or GE in the rat uterus.
Abstract: Phytoestrogens, primarily isoflavones daidzein (DZ) and genistein (GE), are increasingly used by postmenopausal women as an alternative to hormone replacement therapy due to reports that estrogen therapy increases the risk of breast and endometrial cancers. These compounds, as estrogen receptor agonists, may influence chemical carcinogenesis in estrogen-responsive tissues such as the uterus. We utilized ovariectomized (OVX) rats to model menopause and assessed the effects of dietary DZ, GE, or 17β-estradiol (E2) on carcinogen-induced mutagenesis and carcinogenesis in the rat uterus. Big Blue® transgenic rats (derived from Fischer 344 strain) were exposed to 7,12-dimethylbenz[a]anthracene (DMBA) in the presence or absence of the supplements. At 16- or 20-wk sacrifice, the uteri were removed and processed to determine mutant frequencies (MFs) and immunohistochemical or histopathological parameters, respectively. In rats treated with DMBA alone, a significant increase in lacI MFs (P < 0.01) in both...

Journal ArticleDOI
TL;DR: The present study clearly demonstrates the in vivo formation of benzylic-DNA adducts from DMBA, and suggests that hydroxylation of DMBA to form HMBA may be the rate-limiting step for the meso-methyl substitution pathway.
Abstract: Studies were undertaken to determine the formation of benzylic-DNA adducts in rats administered 7,12-dimethylbenz[a]anthracene (DMBA) and its meso-region metabolites by subcutaneous injection. Here, we show that 7-hydroxymethyl-12-methylbenz[a]anthracene (7-HMBA) and 7-sulfoxymethyl-12-methylbenz[a]anthracene (7-SMBA) gave rise to some benzylic-DNA adducts indistinguishable from adducts formed from DMBA. Adducts were analyzed by butanol enrichment-mediated 32P-postlabeling assay. Female Sprague-Dawley rats given a combined dose of 420 micromol DMBA/kg b. wt resulted in two major and up to nine minor adducts in the subcutaneous tissue, with chromatographic resemblance to benzylic-DNA adducts prepared in vitro. Subcutaneous administration of 7-HMBA, 7-SMBA, and 7-methyl-12-hydroxymethylbenz[a]anthracene (12-HMBA) (210, 42, and 210 micromol/kg b. wt, respectively) each resulted in one major and several minor benzylic-DNA adducts. From cochromatography with reference adducts, it was concluded that the benzylic DNA adduct 4, derived from the parent compound, comigrates with the major adduct from 7-HMBA and 7-SMBA, whereas adducts 2 and 3 comigrate with adducts resulting from 12-HMBA and 7-methyl-12-sulfooxymethylbenz[a]anthracene, respectively. These data suggest that 7-sulfooxymethyl- and 12-sulfooxymethy derivatives produce distinct adducts. Several major and minor diol epoxide-related DNA adducts were also detected. The diol epoxide- and benzylic-DNA adducts were found in a 2:1 ratio. The oral, intraperitoneal, and intramammiliary treatments with DMBA showed no detectable benzylic adducts in the liver and mammary glands 24 h after the last treatment, although the adduct formation was clearly evident with SMBA and/or HMBA treatments, suggesting that hydroxylation of DMBA to form HMBA may be the rate-limiting step for the meso-methyl substitution pathway. The present study clearly demonstrates the in vivo formation of benzylic-DNA adducts from DMBA. The data also reveal the involvement of the 12-methyl group of DMBA in adduct formation.

Journal ArticleDOI
TL;DR: Results suggest that HSDB contained at least two constituents of differing polarity that counteracted mammary carcinogenesis.
Abstract: The effect of the heat-dried product of Shochu distillery by-products (HSDB) derived from sweet potato on mammary carcinogenesis in rats was investigated. HSDB was fed at 2.5% or 5% of the total feed weight. Dietary HSDB at the 5% level suppressed the incidence and number of tumors, and delayed the latency of mammary tumor development relative to the control diet. Experiments were conducted to determine the relative polarity of the anticarcinogenic constituent(s). The number of tumors per tumor-bearing rat was lower in the diet group fed with an ethyl acetate extract of HSDB than in the control group. The tumor incidence evaluated at both palpation and autopsy was slightly lower in the group fed with a methanol extract than in the control group. These results suggest that HSDB contained at least two constituents of differing polarity that counteracted mammary carcinogenesis.

Journal ArticleDOI
TL;DR: A lack of influence of estrogen early in life on carcinogenic susceptibility, although the possible impact on mammary carcinogenesis requires further examination is indicated.

Journal ArticleDOI
TL;DR: The results suggest that DMBA can induce gene mutations in heart tissue of OVX rats, and while dietary GE had little or no effect on DMBA‐induced mutation, dietary E2 reduced the mutagenicity of DMBA.
Abstract: In industrialized countries, heart disease rates are higher among women after menopause. Recent studies indicate that consumption of phytoestorogens, e.g., isoflavones such as genistein (GE), may have potential cardiovascular health benefits; however, no studies have evaluated the effect of these agents on toxicant-induced damage in the heart. Since estrogen receptors are found in the heart, and GE mimics estrogenic effects, we have examined whether or not dietary GE or 17 beta-estradiol (E2) modulates the lacI mutant frequency (MF) in the heart of ovariectomized (OVX) Big Blue rats exposed to the model carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Groups of female rats were administered 80 mg/kg DMBA or vehicle by gavage and were chronically fed with diets containing 0, 250, or 1,000 microg/g GE or 5 microg/g E2. Sixteen weeks after carcinogen treatment, the animals were sacrificed and the hearts were removed and processed for determining the frequency and types of mutations in the heart tissue. GE and E2 supplementation alone resulted in nonsignificant increases in MF. The DMBA-induced lacI MF in the heart was sevenfold higher than the control (119.8 +/- 18.7 x 10(-6) vs. 17.4 +/- 3.2 x 10(-6); P T:A (42%) and G:C-->T:A (19%) transversions, followed by G:C-->A:T (13%) and A:T-->G:C (8%) transitions. Feeding E2 altered the DMBA-induced mutational spectra by decreasing A:T-->T:A (23%) and G:C-->T:A (13%) transversions and increasing G:C-->A:T (24%) and A:T-->G:C (21%) transitions. Taken together, the results suggest that DMBA can induce gene mutations in heart tissue of OVX rats, and while dietary GE had little or no effect on DMBA-induced mutation, dietary E2 reduced the mutagenicity of DMBA.

Journal ArticleDOI
TL;DR: The results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA‐inducedmutagenesis in either intact or ovariectomized rats.
Abstract: A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats. Environ. Mol. Mutagen., 2005. Published 2005 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: EGCG has two different suppression mechanisms for DMBA-induced CA depending on the administration time, which may result from the modification of microsomal enzyme system or the inhibition of sulfotransferase activity by EGCG, respectively.
Abstract: The suppressive effect of (-)-epigallocatechin gallate (EGCG), the major polyphenolic constituent present in green tea, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced chromosome aberrations (CA) in rat bone marrow cells was studied. Rats given EGCG before the DMBA injection displayed a considerably suppressed frequency of DMBA-induced CA in their bone marrow cells. The suppressive effect of EGCG (60 mg/kg body weight) given 24 h before was observed 24, 30, 48 and 72 h after the DMBA injection, but not at the early period (6, 12 and 18 h) after the DMBA treatment. On the other hand, EGCG (60 mg/kg body weight) given 0.5 h before DMBA suppressed DMBA-induced CA at all periods after the DMBA injection. The suppression of EGCG given 24 h or 0.5 h before was observed for all doses of DMBA (25, 50, 75 and 100 mg/kg) investigated. EGCG given at 60 mg/kg body weight 0.5 h before the DMBA injection showed greater suppressive effect than the same dose given 24 h before. The suppressive effect of EGCG given 0.5 h before was dosedependent in the range of 20-60 mg/kg body weight. Methyl methanesulfonate (MMS: direct-acting carcinogen)-induced CA were not suppressed by EGCG.The administration of dehydroepiandrosterone (DHEA), a typical substrate for hydroxysteroid sulfotransferases, 0.5 h before DMBA injection also significantly suppressed DMBA-induced CA but DHEA given 24 h before did not.These results suggest that EGCG has two different suppression mechanisms for DMBA-induced CA depending on the administration time. The suppression of DMBA-induced CA by EGCG given 24 h or 0.5 h before may result from the modification of microsomal enzyme system or the inhibition of sulfotransferase activity by EGCG, respectively.

Journal ArticleDOI
TL;DR: It is shown that 7,12-dimethylbenz[a]anthracene-trans-3,4-dihydrodiol rapidly induces mammary cancer by repeated subcutaneous injection in a high proportion of female Sprague-Dawley rats without malignancies at the site of injection, whereas its more lipid soluble diacetate derivative induced injection site sarcomas in addition to distal mammary cancers.

01 Jan 2005
TL;DR: The DMBA-induced mammary tumors can be inhibited when rats were treated with genistein and octylphenol, and the cell differentiation were higher and the proliferation of glandular and atypical hyperplasia were more obvious in groups of GEN and GEN+OP.
Abstract: Objective To investigate the effect of octylphenol and genistein on 7, 12-dimethylbenz[a] anthracene (DMBA)-induced mammary cancer in prepubertal rats. Methods Female SD rats was randomly divided into control group, model group, genistein (GEN) group, octylphenol (OP) group, GEN+OP group. The rats in GEN group, OP group, GEN+OP group were subcutaneously injected with GEN and/or OP from d1 to d7 (the day when the injection began was named as d1, others likewise). DMBA was given to rats except control rats by intragastric administration on d22 and d29. Rats were killed to observe the incidence of breast carcinoma and the changes of histologic pathology on d210, ultrastructure, serum estradiol and progesterone. Results There was no breast tumor in rats of control group. In model group, the incidence of breast carcinoma was 14/21, tumor size and weight were (13.81±2.34) cm~3 and (13.54±2.02) g respectively. In OP group, the incidence of breast carcinoma was 20/21(P0.05). In the groups of GEN and GEN+OP, the incidence of breast tumor were 7/21 (P0.05) and 12/21 respectively, tumor size (3.8±2.3) cm~3 and (4.4±3.7) cm~3 respectively, tumor weight (4.3±3.4) g and (5.3±4.2) g respectively. Histological and ultrastructural analysis showed that cell differentiation were lower in OP group. The cell differentiation were higher and the proliferation of glandular and atypical hyperplasia were more obvious in groups of GEN and GEN+OP. Conclusion Octylphenol maybe accelerate DMBA-induced mammary tumors and genistein can inhibit DMBA-induced breast tumors. The DMBA-induced mammary tumors can be inhibited when rats were treated with genistein and octylphenol.