Abstract:
:Weanling male F344 rats were fed either a semi-purified diet low in methionine and lacking in choline and folic acid (folate/methyl deficient) or a supplemented control diet for periods of 2, 5, 7 days, 3 weeks, and 9 weeks. Two days after initiating the folate/methyl deficient diet in weanling F344 rats, the incidence of apoptotic bodies, identified by in situ end-labeling of 3'-OH DNA strand breaks, was significantly increased in liver sections from the deficient rats. Apoptotic cell death was confirmed biochemically by an increase in nuclear Ca2+/Mg2+-dependent endonuclease activity that paralleled the increase in apoptotic bodies over the 9-week feeding period. There was no morphologic evidence of necrotic foci or necrosis-associated inflammatory response over the 9-week period. Confirming that cell turnover is chronically elevated in this model, the increase in apoptotic rate was accompanied by a sustained increase in the mitotic index (MI). The DNA repair-associated enzyme, poly(ADPribose) polymerase (PARP), was similarly elevated and was associated with significant decreases in the substrate for ADPribose polymer synthesis, nicotinamide adenine dinucleotide (NAD). Because folate metabolites are essential for de novo purine and thymidine biosynthesis, prolonged deficiency in folic acid can induce an imbalance in the deoxynucleotide precursors for DNA replication/repair and negatively affect the fidelity of DNA synthesis. Using an HPLC method, hepatic deoxyuridine triphosphate (dUTP) levels were increased at 3 and 9 weeks after initiation of the deficient diet and levels of thymidine triphosphate (dTTP) were reduced. An increase in dUTP/ dTTP ratio is consistent with a block in folate-dependent de novo thymidylate biosynthesis and may predispose to uracil misincorporation and DNA repair-related DNA strand breaks.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
James SJ,Miller BJ,Basnakian AG,Pogribny IP,Pogribna M,Muskhelishvili Ldoi
10.1093/carcin/18.2.287subject
Has Abstractpub_date
1997-02-01 00:00:00pages
287-93issue
2eissn
0143-3334issn
1460-2180journal_volume
18pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::SH3RF (SH3-domain-containing RING finger protein) family members, SH3RF1-3, are multidomain scaffold proteins involved in promoting cell survival and apoptosis. In this report, we show that SH3RF2 is an oncogene product that is overexpressed in human cancers and regulates p21-activated kinase 4 (PAK4) protein stabilit...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt338
更新日期:2014-03-01 00:00:00
abstract::Apigenin, a flavonoid abundant in various vegetables and fruits, including parsley and onions, has been reported to possess anticarcinogenic effects. However, the direct molecular target of apigenin and its chemopreventive effect on ultraviolet (UV)-induced skin inflammation are not understood fully. Herein, we examin...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs358
更新日期:2013-02-01 00:00:00
abstract::Gestational trophoblastic diseases (GTD) are group of pregnancy-related tumors characterized by abnormal levels of 'β-hCG' with higher incidence in South-East Asia, especially India. Our laboratory has reported that wild-type BRCA1 transcriptionally regulates β-hCG in triple negative breast cancers (TNBCs). These fact...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgz117
更新日期:2020-07-10 00:00:00
abstract::An enhancement of the cellular cAMP level has been shown to protect against phorbol ester-induced inhibition of gap junctional intercellular communication (GJIC) and induction of morphological transformation in Syrian hamster embryo (SHE) cells. Cholera toxin, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and theophyl...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.10.1803
更新日期:1992-10-01 00:00:00
abstract::Germline genetic variability might contribute, at least partially, to the survival of pancreatic ductal adenocarcinoma (PDAC) patients. Two recently performed genome-wide association studies (GWAS) on PDAC overall survival (OS) suggested (P < 10(-5)) the association between 30 genomic regions and PDAC OS. With the aim...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgw080
更新日期:2016-10-01 00:00:00
abstract::17beta-estradiol (E2), estrone and diethylstilbestrol (DES) had no effect on nuclear and nucleolar RNA synthesis in vitro. However, after reacting with dimethyldioxirane (DMDO), a versatile epoxide-forming oxidant, these estrogens were able to inhibit and in a dose-dependent manner nuclear and nucleolar RNA synthesis ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/17.9.1957
更新日期:1996-09-01 00:00:00
abstract::Nitrosamine-induced hepatocarcinogenesis has been used to investigate the regulation and expression of different drug-metabolizing enzymes in preneoplastic and neoplastic lesions in the female Wistar rat. The enzymes investigated were two phenobarbital-inducible cytochrome P-450 (cyt. P-450) isoenzymes (PB1 and PB2, m...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.4.513
更新日期:1985-04-01 00:00:00
abstract::The purpose of this work was to study the relative activities and stabilities of phase-I and phase-II drug metabolizing enzymes in incubation mixtures used in vitro genotoxicity testing in order to optimize the conditions of the assay, increase sensitivity and eliminate false negative results. Cytochrome P-450, NADPH-...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.9.1179
更新日期:1987-09-01 00:00:00
abstract::Precursor T-cell lymphoblastic neoplasms are aggressive malignancies in need for more effective and specific therapeutic treatments. A significant fraction of these neoplasms harbor deletions on the locus 9p21, targeting the tumor suppressor CDKN2A but also deleting the aconitase 1 (ACO1) gene, a neighboring housekeep...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgz185
更新日期:2020-08-12 00:00:00
abstract::To compare mutagenesis by O6-methylguanine (m6G), O4-methylthymine (m4T) and O6-ethylguanine (e6G), and assess their genotoxicity in Escherichia coli, double-stranded and gapped plasmids were constructed containing a single m6G, e6G or m4T in the initiation codon (ATG) of a lacZ' gene. Modified base induced mutations ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.3.457
更新日期:1998-03-01 00:00:00
abstract::As rat tracheal epithelial cells progress from a normal to a neoplastic phenotype there are systematic changes in their ability to produce and activate latent transforming growth factor type beta (TGF-beta) as well as systematic changes in their response to this growth factor. Using a TGF-beta radioreceptor binding co...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.6.973
更新日期:1989-06-01 00:00:00
abstract::Rats received a choline-deficient diet containing 0.1% (w/w) DL-ethionine (CDE) for 4, 10, 14 or 22 weeks. A separate group was treated for 4 weeks with CDE and then received a normal diet for 4 weeks. The L and M2 isoenzymes of pyruvate kinase were immunocytochemically demonstrated in liver sections. L-PK expression ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.1.99
更新日期:1998-01-01 00:00:00
abstract::Mevastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. Butyrate, a short-chain fatty acid, reduces proliferation and induces differentiation of human colon cancer cells. The aim of our study was to determine the effect of mevastatin, ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/22.7.1061
更新日期:2001-07-01 00:00:00
abstract::Previous studies have shown that 1- and 3-nitrobenzo[a]pyrene (NBaP) were mutagenic in the Salmonella reversion assay without exogenous activation and that 1-, 3- and 6-NBaP were mutagenic in the presence of hepatocytes or liver homogenate (S9). In the present study, 1-, 3- and 6-NBaP were tested for mutagenicity in C...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.4.681
更新日期:1986-04-01 00:00:00
abstract::Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.10% DL-ethionine for up to 30 weeks. Liver slices from rats killed 4, 6, 10, 14, 22 and 30 weeks after starting the treatment were histochemically analyzed for the following parameters: basophilia, expression of cytokeratin 19 (which in th...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.2.225
更新日期:1991-02-01 00:00:00
abstract::The mutagenicities of 2-aminodipyrido [1,2-a:3',2'-d] imidazole (Glu-P-2, a mutagen obtained from pyrolysate of glutamic acid) and six methyl substituted derivatives of Glu-P-2 were tested with Salmonella typhimurium TA98 and TA100 with S-9 mix. Glu-P-1 (6-Me-Glu-P-2) was the strongest mutagen to TA98 and TA100. 3-Me-...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/1.11.889
更新日期:1980-01-01 00:00:00
abstract::Deregulated microRNAs (miRNAs) and their roles in cancer development have attracted much attention. Two miRNAs, miR-15a and miR-16, which act as putative tumor suppressor by targeting the oncogene BCL2, have been implicated in cell cycle, apoptosis and proliferation. In this study, we investigated the possible role ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs333
更新日期:2013-02-01 00:00:00
abstract::Zinc has been shown to be accumulated in N-methyl-N-nitrosourea (MNU)-induced rat mammary tumors. Zinc is required for cell proliferation and tumorigenesis is characterized by dysregulation of cell proliferation. An accumulation of zinc in mammary tumors perhaps indicates a reliance on zinc to sustain tumor growth. Li...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgh214
更新日期:2004-10-01 00:00:00
abstract::Mouse ovarian surface epithelial cells (MOSEC) were obtained from virgin, mature mice by mild trypsinization and were repeatedly passaged in vitro. Early passage cells (<20 passages) exhibited a cobblestone morphology and contact inhibition of growth. After approximately 20 passages in vitro, cobblestone morphology an...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.4.585
更新日期:2000-04-01 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
abstract::Resveratrol is a phytochemical that has been under consideration for use as a prostate cancer chemopreventive agent. However, the efficacy, as well as the mechanisms of action of resveratrol on prostate cancer prevention, remains largely unknown. This study seeks to address these questions and examine the cancer preve...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn131
更新日期:2008-10-01 00:00:00
abstract::We demonstrated previously that growth factor receptor-bound protein 2 (Grb2) associates with the transforming growth factor-beta (TGF-beta) type II receptor [TbetaR-II] upon its phosphorylation on Tyr284 by Src. Although this phosphotransferase reaction is critical in mediating TGF-beta stimulation of epithelial-mese...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgm245
更新日期:2008-02-01 00:00:00
abstract::The high incidence of oesophageal cancer in Northern Iran has been associated with opium. N-Nitrosamines are the only carcinogens known to induce oesophageal cancer in animals. Ethanol, which is the major influence on oesophageal cancer incidence in the West, inhibits the first pass clearance of N-nitrosodimethylamine...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.2.365
更新日期:1997-02-01 00:00:00
abstract::The role of parity before and after N-methyl-N-nitrosourea (MNU) treatment in protection against mammary carcinogenesis was investigated. The effect of lactation on reduction in the incidence of mammary carcinoma was also examined. Parous rats were compared with respective age-matched virgins (AMVs). Pregnancy and lac...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.4.623
更新日期:1999-04-01 00:00:00
abstract::Normal human fibroblasts do not synthesize platelet-derived growth factor (PDGF), but they respond to its mitogenic action. In contrast, cells from several human fibrosarcomas have been shown to synthesize PDGF at significant levels. To investigate the possible role of PDGF expression in the development of tumors of m...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.10.2167
更新日期:1994-10-01 00:00:00
abstract::The urinary excretion of dimethylnitrosamine (DMN) was studied in male Sprague-Dawley rats. Animals were given DMN (3, 5, 10, 20, 30 and 50 mg/kg body weight, i.p.) or [3H]DMN (0.1, 1 and 3 mg; 8.7, 1.5 and 0.28 mCi/kg body weight, respectively, i.p.) diluted with sterile 0.9% NaCl. Urine was collected for 24 h after ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.7.609
更新日期:1981-01-01 00:00:00
abstract::Treatment of human skin fibroblasts in early S-phase with (+-)7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE-I) results in more extensive modification of early replicating DNA than parental DNA. We have investigated the effects of benzamide (BZ) and 3-aminobenzamide (3-ABZ), i...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.3.489
更新日期:1992-03-01 00:00:00
abstract::Most cancer cells show resistance to ionizing radiation (IR)-induced cell death. Recently, Ki-Ras was reported to be responsible for the increased radioresistance. We report here that inhibition of IR-induced activaton of nuclear transcription factor kappa B (NF-kappaB) but not of either Akt or MAPK kinase (MEK), incr...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi081
更新日期:2005-08-01 00:00:00
abstract::The rates of reaction and the products formed when two vicinal diol-epoxides derived from benz(a)anthracene, anti-BA-3,4-diol 1,2-oxide (t-3,r-4-dihydroxy-t-1,2-oxy-1,2,3,4-tetrahydrobenz(a) anthracene)* and anti-BA-8,9-diol 10,11-oxide (r-8,t-9-dihydroxy-t-10,11-oxy-8,9,10,11-tetrahydrobenz(a)anthracene) reacted with...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/1.3.277
更新日期:1980-03-01 00:00:00
abstract::O6-Methylguanine-DNA methyltransferase (MT)-proficient Chinese hamster ovary cells were grown in the presence of low, gradually increasing levels of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) with the aim of selecting MNNG-resistant cell lines. Six resistant clones with two levels of resistance were isolated. A 3-fol...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.7.1217
更新日期:1988-07-01 00:00:00