Abstract:
:Isoflavone genistein is a specific inhibitor of protein tyrosine kinase (PTK) and has been shown to have a variety of anticancer activities in cultured cells and animal models. We report here that genistein significantly inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-promoted skin tumorigenesis in a two-stage carcinogenesis model. In an initiation study, 10 micromol genistein was applied daily to female SENCAR mouse skin for 1 week, followed by initiation with 10 nmol DMBA. Mice were then treated with twice weekly 4 microg TPA. Genistein was shown to reduce tumor incidence and multiplicity in DMBA-initiated skin tumors by approximately 20 (P < 0.05) and 50% (P < 0.01), respectively. Two promotion studies were conducted using CD-1 and SENCAR mice. In experiment 1, CD-1 mice were initiated with 100 nmol DMBA and followed by a twice weekly regimen of 1 and 5 micromol genistein/4 microg TPA. In experiment 2, SENCAR mice were initiated with 10 nmol DMBA and followed by a regimen of 5, 10 and 20 micromol genistein/2 microg TPA. Both studies consistently showed that genistein substantially inhibited TPA-promoted skin tumorigenesis by reducing the tumor multiplicity by approximately 60 and 75%, respectively (P < 0.01). However, the tumor incidence appeared to be less affected. Mechanistic studies showed that genistein inhibited DMBA-induced bulky DNA adduct formation and substantially suppressed TPA-stimulated H2O2 and inflammatory responses in mouse skin by >60% (P < 0.01). In contrast, genistein only exhibited a moderate inhibition of TPA-induced ornithine decarboxylase activity (P > 0.05). Our results suggest that genistein exerts its anti-initiational and anti-promotional effects on skin carcinogenesis probably through blockage of DNA adduct formation and inhibition of oxidative and inflammatory events in vivo.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Wei H,Bowen R,Zhang X,Lebwohl Mdoi
10.1093/carcin/19.8.1509subject
Has Abstractpub_date
1998-08-01 00:00:00pages
1509-14issue
8eissn
0143-3334issn
1460-2180journal_volume
19pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::The effect of a deoxycholic acid instillation on colonic epithelium was investigated and compared with the effect of an intervention scheme in which deoxycholic acid (DCA) treated mice received oral supplements of calcium lactate. The morphology of colonic tissue exposed to DCA was markedly affected when compared to t...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.9.1205
更新日期:1983-09-01 00:00:00
abstract::Catechol (1,2-dihydroxybenzene) is a major phenolic compound present in the co-carcinogenic fraction of cigarette tar. It has been shown to be a potent co-carcinogen with benzo[a]pyrene (BaP) in mouse skin. In this study we have examined the co-carcinogenic and co-initiating activities of catechol with racemic and ena...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.10.1897
更新日期:1989-10-01 00:00:00
abstract::The polypeptide hormone epidermal growth factor (EGF) has been shown to enhance adenovirus type 5 transformation of a cloned culture of rat embryo cells (CREF) and X-ray or u.v.-light induced transformation of 10T1/2 mouse embryo cells. In both systems, the degree of enhancement was quantitatively similar to that obse...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.3.183
更新日期:1981-01-01 00:00:00
abstract::Cigarette smoking is a major cause of human cancer at a variety of sites, although its carcinogenic mechanisms remains unestablished. Cigarette smoke can be divided into two phases, gas phase and particulate matter (tar). Both phases contain high concentrations of oxidants and free radicals, especially nitric oxide (N...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.7.1359
更新日期:1997-07-01 00:00:00
abstract::Pancreatic cancer has remained refractory to treatment. In large part, this results from the lack of an animal model that mimics pancreatic cancer in man. We describe a novel experimental model of pancreatic cancer that shares the genetic background, histologic features and natural history of human mixed acinar-ductal...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgx119
更新日期:2018-02-09 00:00:00
abstract::The E6/E7 oncoproteins of human papillomavirus (HPV) types 16 and 18 are responsible for the efficient immortalization of human genital keratinocytes and we have recently reported that such immortalized cells display alterations in the expression of cyclin A, cyclin B, and cdc-2. To determine whether these alterations...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/17.7.1395
更新日期:1996-07-01 00:00:00
abstract::Genomic alterations affecting components of the mechanistic target of rapamycin (mTOR) pathway are found rather frequently in cancers, suggesting that aberrant pathway activity is implicated in oncogenesis of different tumor types. mTOR functions as the core catalytic kinase of two distinct complexes, mTOR complex 1 (...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/bgy086
更新日期:2018-07-30 00:00:00
abstract::Alternative splicing regulators have emerged as new players in cancer development, modulating the activities of many tumor suppressors and oncogenes and regulating the signaling pathways. However, little is known about the mechanisms by which these oncogenic splicing factors lead to cellular transformation. We have sh...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt247
更新日期:2013-11-01 00:00:00
abstract::In order to establish an animal model for studying the cause and prevention of esophageal adenocarcinoma (EAC) and its frequent precursor, Barrett's esophagus (BE), factors affecting the pathogenic processes were investigated in an esophagoduodenal anastomosis model with rats. Experiments by us and others have shown t...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.11.2265
更新日期:1997-11-01 00:00:00
abstract::The MDM2 protein negatively regulates p53 expression level in modulating DNA repair, cell-cycle control, cell growth and apoptosis. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter protein expression and may, thus, play a role in carcinogenesis. To test our hypothesis that the MDM2 promot...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl047
更新日期:2006-10-01 00:00:00
abstract::Cytochrome P4501A1 (CYP1A1) has been implicated in the conversion of numerous polycyclic aromatic hydrocarbons into electrophilic species capable of binding covalently to DNA and has therefore been postulated to be involved in the initiation of carcinogenesis. The expression of CYP1A1 protein appears not to be constit...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.8.1361
更新日期:1998-08-01 00:00:00
abstract::The arylamine carcinogen 3,2'-dimethyl-4-aminobiphenyl (DMABP) has been proposed to be metabolically activated to DNA-binding derivatives through the formation of an N-hydroxy intermediate. In this study, the subsequent activation of N-hydroxy-DMABP through acid catalysis or enzymatic esterification was examined. [Rin...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.2.251
更新日期:1985-02-01 00:00:00
abstract::An important difference between chemical agents that induce oxidative damage in DNA and ionizing radiation is that radiation-induced damage is clustered locally on the DNA. Both modelling and experimental studies have predicted the importance of clustering of lesions induced by ionizing radiation and its dependence on...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.5.905
更新日期:1999-05-01 00:00:00
abstract::The mutational specificity of the monofunctional alkylating agent N-propyl-N'-nitro-N-nitrosoguanidine (PNNG) has been determined through the DNA sequence characterization of 109 LacI- mutations of Escherichia coli. The predominant mutation induced was the G:C----A:T transition (73%), presumably the result of O6-propy...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.5.949
更新日期:1989-05-01 00:00:00
abstract::Dietary-related indoles, isothiocyanates, and the allyl isothiocyanate glucosinolate, sinigrin, were administered to F344 rats in the diet for 2 weeks (chronic protocol) or by gavage 2 h before sacrifice (acute protocol) and the effects of these pretreatments on the alpha-hydroxylation of two carcinogenic nitrosamines...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.4.539
更新日期:1985-04-01 00:00:00
abstract::DNA repair after gamma radiation was studied in purified T lymphocytes from young and aged subjects. Two different assays were employed. In the first, T lymphocytes were stimulated with phytohemagglutinin (PHA) for 72 h and then treated with hydroxyurea, irradiated with 30 K rads and pulsed with [3H]thymidine (TdR) fo...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/3.1.45
更新日期:1982-01-01 00:00:00
abstract::BALB/c 3T3 A31-1-13 cells are highly susceptible to chemical-induced cell transformation and their gap-junctional intercellular communication (GJIC) is decreased when these cells become confluent. On the other hand, A31-1-1 cells do not show such a change in GJIC and are more resistant to chemical induction of transfo...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.10.1923
更新日期:1991-10-01 00:00:00
abstract::The formation of thioether conjugates is an important pathway for inactivation of certain carcinogens. This study assessed the mechanism by which the bladder carcinogen 2-amino-4-(5-nitro-2-furyl)-thiazole (ANFT) forms a glutathione conjugate (ANFT-SG). Peroxidatic metabolism of ANFT, in the presence of glutathione, r...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.11.2087
更新日期:1992-11-01 00:00:00
abstract::To determine whether B or T lymphoid malignancies could be induced following the exposure of lymphoid cells within different lymphoid organs to a potential chemical carcinogen, 3-methylcholanthrene (3-MC) was directly injected into surgically exposed Peyer's patches (PP), mesenteric lymph nodes (MLN), axillary lymph n...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.8.1257
更新日期:1986-08-01 00:00:00
abstract::Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers, and most patients develop chemoresistance after first-line treatments. Despite recent advances, the 5-year relative survival is ~45% for all OC subtypes, and invasive epithelial OC has only a 17% survival rate when diagnosed at a late sta...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/bgx054
更新日期:2017-10-01 00:00:00
abstract::Chemotherapeutic agents have been the mainstay of cancer therapy for years. However, their effectiveness has been limited by toxicities they impart on normal cells. Staurosporine (ST) has been shown to arrest normal, but not breast cancer, cells in G1. Therefore, ST may become a chemoprotective agent, arresting normal...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt186
更新日期:2013-10-01 00:00:00
abstract::Interleukin 6 (IL6) is a key cytokine involved in the development and progression of inflammation-associated hepatocellular carcinoma (HCC). However, the mechanisms of IL6 action on HCC remain largely unknown. Proton and Ca(2+) are two intracellular messenger ions, which are believed to play a central role in tumorige...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgw004
更新日期:2016-03-01 00:00:00
abstract::Non-steroidal anti-inflammatory drugs prevent colorectal cancer by inhibiting cyclooxygenase (COX) enzymes that synthesize tumor-promoting prostaglandins. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a tumor suppressor that degrades tumor-promoting prostaglandins. Murine knockout of 15-PGDH increases susceptibil...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgu241
更新日期:2015-02-01 00:00:00
abstract::The syn- and anti-isomers of 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-methylchrysene (6-MeC-1,2-diol-3,4-epoxide) were synthesized and their mutagenic activities in Salmonella typhimurium were compared with those of the syn- and anti-isomers of 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (5-MeC-1,2...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.12.2067
更新日期:1986-12-01 00:00:00
abstract::Pardaxin, an antimicrobial peptide secreted by the Red Sea flatfish Pardachirus marmoratus, inhibits proliferation and induces apoptosis of human cancer cell lines. However, the underlying molecular mechanisms are only partially understood at present. In this study, we used proteomic approaches and network reconstruct...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt130
更新日期:2013-08-01 00:00:00
abstract::Transgenic mice containing one copy of hepatitis B virus (HBV) genome without the core gene and expressing hepatitis B surface antigen (HBsAg) were crossed with C3H/He mice. The F1 hybrids (approximately 50% HBV positive and approximately 50% HBV negative) were treated with a single dose of diethylnitrosamine (NDEA) o...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.6.953
更新日期:1990-06-01 00:00:00
abstract::The Manchester (England) Children's Tumour Registry is population-based with a high level of ascertainment. Pathologic review ensured diagnostic accuracy. Routine monitoring of annual incidence revealed a significant increase in germ cell tumours from approximately 1 per million person years to approximately 4. Analys...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/3.1.75
更新日期:1982-01-01 00:00:00
abstract::The hypolipidaemic drug nafenopin (NAF) has been shown to enhance the hepatocarcinogenic effect of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine in rats. We have investigated whether the NAF-induced peroxisome proliferation in hepatocytes interferes with NDMA's metabolism and interaction with DNA. Adult male...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.9.1309
更新日期:1985-09-01 00:00:00
abstract::The effects of hyperoxia on lung tumor development were examined in mice and rats. In mice, exposure to 70% O2 prevented the development of urethan- or 3-methylcholanthrene-induced lung tumors. Dietary antioxidants [butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA)] were unable to prevent the inhibitio...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.9.1581
更新日期:1986-09-01 00:00:00
abstract::Genome-wide DNA hypomethylation was one of the first epigenetic alterations described in cancer cells. However, the cause of this hypomethylation is still poorly understood. We have previously developed a line of primary mesenchymal stem cells (MSC, the putative origin of various types of sarcoma) in which five oncoge...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq080
更新日期:2010-10-01 00:00:00