Dose-response studies of MeIQx in rat liver and liver DNA at low doses.

Abstract:

:2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a heterocyclic amine mutagen found in cooked meats and is carcinogenic in mice and rats at high doses (mg/kg body wt). Humans, however, are exposed to low amounts (p.p.b.) in the diet, and the effects caused by exposure to human equivalent doses of MeIQx have been difficult to determine accurately. We report on the effect of MeIQx exposure on liver bioavailability, hepatic DNA binding and MeIQx persistence in both liver tissue and liver DNA after acute (24 h), and subchronic (7 day and 42 day) exposures in male Sprague-Dawley rats. Male Sprague-Dawley rats were administered [2-14C]MeIQx either by gavage or in the diet for 1, 7 or 42 days (1 x 10(-6) mg/kg day up to 3.4 x 10(-2) mg/kg day dose) and the [2-14C]MeIQx was measured by accelerator mass spectrometry (AMS). Assessment of the kinetics of hepatic MeIQx DNA adduct formation over 42 days (1.1 x 10(-4) mg [2-14C]MeIQx kg daily dose) shows that steady-state [2-14C]MeIQx tissue concentrations of 138 +/- 15 pg/g liver and DNA adduct levels of 113 +/- 10 ag adduct/micrograms DNA were reached at 14-28 days and 28 days respectively. The relationship between administered dose and either hepatic MeIQx DNA adduct levels or MeIQx tissue levels are linear for the 24 h, 7 day and 42 day exposures. Furthermore, MeIQx adducts persist for at least 14 days after exposure ceases. These data suggest that bioavailability and DNA adduction by MeIQx increase linearly with increasing dose for both acute and subchronic exposures. These data also show that MeIQx DNA adducts are useful in predicting daily exposure and support a linear extrapolation in the risk assessment of MeIQx. However, the quantitative relationship between DNA adducts and tumor formation will also depend on the specific tissue and the subsequent steps needed for tumor progression.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Frantz CE,Bangerter C,Fultz E,Mayer KM,Vogel JS,Turteltaub KW

doi

10.1093/carcin/16.2.367

subject

Has Abstract

pub_date

1995-02-01 00:00:00

pages

367-73

issue

2

eissn

0143-3334

issn

1460-2180

journal_volume

16

pub_type

杂志文章
  • Synthetic D-amino acid peptide inhibits tumor cell motility on laminin-5.

    abstract::Cell motility is partially dependent on interactions between the integrins and the extracellular matrix. Our previous studies have identified synthetic D-amino acid cell adhesion peptides using a combinatorial screening approach. In this study, we demonstrate that HYD1 (kikmviswkg) completely blocks random haptotactic...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgl005

    authors: Sroka TC,Pennington ME,Cress AE

    更新日期:2006-09-01 00:00:00

  • v-sis oncogene-induced transformation of human fibroblasts into cells capable of forming benign tumors.

    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

    authors: Yang D,Kohler SK,Maher VM,McCormick JJ

    更新日期:1994-10-01 00:00:00

  • DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker.

    abstract::Using whole blood from 15 twin pairs discordant for breast cancer and high-resolution (450K) DNA methylation analysis, we identified 403 differentially methylated CpG sites including known and novel potential breast cancer genes. Confirming the results in an independent validation cohort of 21 twin pairs determined th...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs321

    authors: Heyn H,Carmona FJ,Gomez A,Ferreira HJ,Bell JT,Sayols S,Ward K,Stefansson OA,Moran S,Sandoval J,Eyfjord JE,Spector TD,Esteller M

    更新日期:2013-01-01 00:00:00

  • Cooperation of bcl-2 and myc in the neoplastic transformation of normal rat liver epithelial cells is related to the down-regulation of gap junction-mediated intercellular communication.

    abstract::The objectives of this study were to isolate several rat liver epithelial cell clones containing the human bcl-2 and myc/bcl-2 genes in order to study their potential cooperative effect on neoplastic transformation and gap junction-mediated intercellular communication (GJIC) and to test the hypothesis that the loss of...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:

    authors: DeoCampo ND,Wilson MR,Trosko JE

    更新日期:2000-08-01 00:00:00

  • Multiple cutaneous basal cell carcinomas: glutathione S-transferase (GSTM1, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) polymorphisms influence tumour numbers and accrual.

    abstract::The genetic factors that mediate the pathogenesis of multiple primary cutaneous basal cell carcinomas (BCC) are largely unclear. Thus, some patients suffer many BCC (>30) and/or rapid accrual (number of tumours/year from first presentation) of further lesions. We have studied, in 827 English Caucasians, the influence ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.9.1891

    authors: Lear JT,Heagerty AH,Smith A,Bowers B,Payne CR,Smith CA,Jones PW,Gilford J,Yengi L,Alldersea J,Fryer AA,Strange RC

    更新日期:1996-09-01 00:00:00

  • The metabolism and activation of polycyclic aromatic hydrocarbons in epithelial cell aggregates and fibroblasts prepared from rat mammary tissue.

    abstract::The metabolism of 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (BP) and benz[a]anthracene (BA) by epithelial cell aggregates and fibroblasts in culture has been investigated using mammary tissue obtained from female Wistar rats. The results show that: (a) both types of mammary cells metabolise all three hydro...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.2.203

    authors: Cooper CS,Pal K,Hewer A,Grover PL,Sims P

    更新日期:1982-01-01 00:00:00

  • Over-expression of EphB3 enhances cell-cell contacts and suppresses tumor growth in HT-29 human colon cancer cells.

    abstract::Receptor tyrosine kinase EphB3 is expressed in cells in the bottom of intestinal crypts near stem cell niches. Loss of Ephb3 has recently been reported to produce invasive colorectal carcinoma in Apc(Min/+) mice and EphB-mediated compartmentalization was demonstrated to be a mechanism suppressing colorectal cancer pro...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgp133

    authors: Chiu ST,Chang KJ,Ting CH,Shen HC,Li H,Hsieh FJ

    更新日期:2009-09-01 00:00:00

  • Expression of cytochrome P450 and microsomal epoxide hydrolase in cervical and oral epithelial cells immortalized by human papillomavirus type 16 E6/E7 genes.

    abstract::Epidemiological evidence suggests that the presence of human papillomaviruses (HPV), when combined with smoking behaviors, considerably enhances the risk of developing oral, cervical, vulvar, and/or anal carcinomas. It is well established that the cytochrome P450 (CYP), microsomal epoxide hydrolase (mEH), and other bi...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.6.1391

    authors: Farin FM,Bigler LG,Oda D,McDougall JK,Omiecinski CJ

    更新日期:1995-06-01 00:00:00

  • Fractionation of grape seed extract and identification of gallic acid as one of the major active constituents causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells.

    abstract::The anti-cancer efficacy of grape seed extract (GSE) against prostate cancer (PCA) via its anti-proliferative, pro-apoptotic and anti-angiogenic activities in both cell culture and animal models have recently been described by us. GSE is a complex mixture containing gallic acid (GA), catechin (C), epicatechin (EC) and...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi347

    authors: Veluri R,Singh RP,Liu Z,Thompson JA,Agarwal R,Agarwal C

    更新日期:2006-07-01 00:00:00

  • Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives.

    abstract::Garcinol, a polyisoprenylated benzophenone, from the fruit rind of Garcinia spp., has been shown to have anti-inflammatory and anticarcinogenic activities. To study its mechanism of action, we analyzed the effects of garcinol and its derivatives, including cambogin, garcim-1 and garcim-2, on arachidonic acid metabolis...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi208

    authors: Hong J,Sang S,Park HJ,Kwon SJ,Suh N,Huang MT,Ho CT,Yang CS

    更新日期:2006-02-01 00:00:00

  • Epidermal papillomas and carcinomas induced in uninitiated mouse skin by tumor promoters alone contain a point mutation in the 61st codon of the Ha-ras oncogene.

    abstract::Previous results in a number of laboratories have demonstrated that epidermal papillomas and carcinomas induced by the two-stage protocol of initiation and promotion contain a point mutation in the 61st codon of the c-Ha-ras oncogene when the initiating agent used is 7,12-dimethylbenz[a]anthracene (DMBA). In the prese...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/9.4.665

    authors: Pelling JC,Neades R,Strawhecker J

    更新日期:1988-04-01 00:00:00

  • Modulation of glutathione content and the effect on methionine auxotrophy and cellular distribution of homocysteine and cysteine in mouse cell lines.

    abstract::The inability of cells in culture to grow in medium where methionine is replaced by its metabolic precursor, homocysteine, has been linked to neoplastic transformation and termed 'methionine dependence' or 'methionine auxotrophy'. The present investigation was undertaken to establish the influence of intracellular glu...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.2.241

    authors: Djurhuus R,Svardal AM,Mansoor MA,Ueland PM

    更新日期:1991-02-01 00:00:00

  • Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1 driven breast cancer.

    abstract::The cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) (p27) is a marker of prognosis in many cancers, including breast cancer. Low p27 expression correlates with poor prognosis, especially in hormone receptor positive breast tumors. This association suggests a role for p27 in hormone-dependent cancer. We used the Wnt-...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgp089

    authors: Glover CE,Gurley KE,Kim KH,Storer B,Fero ML,Kemp CJ

    更新日期:2009-06-01 00:00:00

  • Resveratrol protects mouse embryonic stem cells from ionizing radiation by accelerating recovery from DNA strand breakage.

    abstract::Resveratrol has elicited many provocative anticancer effects in laboratory animals and cultured cells, including reduced levels of oxidative DNA damage, inhibition of tumor initiation and progression and induction of apoptosis in tumor cells. Use of resveratrol as a cancer-preventive agent in humans will require that ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr236

    authors: Denissova NG,Nasello CM,Yeung PL,Tischfield JA,Brenneman MA

    更新日期:2012-01-01 00:00:00

  • DNA--protein crosslinks, a biomarker of exposure to formaldehyde--in vitro and in vivo studies.

    abstract::Formaldehyde (FA) is a widely produced industrial chemical. Sufficient evidence exists to consider FA as an animal carcinogen. In humans the evidence is not conclusive. DNA-protein crosslinks (DPC) may be one of the early lesions in the carcinogenesis process in cells following exposures to carcinogens. It has been sh...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.1.121

    authors: Shaham J,Bomstein Y,Meltzer A,Kaufman Z,Palma E,Ribak J

    更新日期:1996-01-01 00:00:00

  • Relationship of serum selenium levels to tumor activity in acute non-lymphocytic leukemia.

    abstract::Serum selenium (Se) levels were measured before, during and after high-dose induction chemotherapy in 70 patients with acute non-lymphocytic leukemia (ANLL). Pre-treatment serum Se levels were lower in patients than in controls (0.082 +/- 0.033 micrograms/ml versus 0.097 +/- 0.035 micrograms/ml, P less than 0.01). Pre...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/10.11.2089

    authors: Beguin Y,Bours V,Delbrouck JM,Robaye G,Roelandts I,Bury J,Fillet G,Weber G

    更新日期:1989-11-01 00:00:00

  • SAA1 is upregulated in gastric cancer-associated fibroblasts possibly by its enhancer activation.

    abstract::Cancer-associated fibroblasts (CAFs) tend to have tumor-promoting capacity, and can provide therapeutic targets. Even without cancer cells, CAF phenotypes are stably maintained, and DNA methylation and H3K27me3 changes have been shown to be involved. Here, we searched for a potential therapeutic target in primary CAFs...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgaa131

    authors: Yasukawa Y,Hattori N,Iida N,Takeshima H,Maeda M,Kiyono T,Sekine S,Seto Y,Ushijima T

    更新日期:2020-12-07 00:00:00

  • Quinol diglucuronides are predominant conjugated metabolites found in bile of rats following intratracheal instillation of benzo[a]pyrene.

    abstract::[3H]Benzo[a]pyrene (B[a]P) was administered to male Sprague-Dawley rats via intratracheal instillation, and bile was collected over a period of 6 h. Conjugated metabolites of B[a]P in bile were separated by paper chromatography or reversed-phase ion-pair HPLC and quantified by liquid scintillation spectrometry. In pap...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/13.3.403

    authors: Bevan DR,Sadler VM

    更新日期:1992-03-01 00:00:00

  • GBP-1 acts as a tumor suppressor in colorectal cancer cells.

    abstract::The human guanylate-binding protein 1 (GBP-1) is among the proteins the most highly induced by interferon-γ (IFN-γ) in every cell type investigated as yet. In vivo, GBP-1 expression is associated with the presence of inflammation and has been observed in autoimmune diseases, inflammatory bowel diseases (IBD) and cance...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs310

    authors: Britzen-Laurent N,Lipnik K,Ocker M,Naschberger E,Schellerer VS,Croner RS,Vieth M,Waldner M,Steinberg P,Hohenadl C,Stürzl M

    更新日期:2013-01-01 00:00:00

  • 3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial.

    abstract::Women who carry the BRCA mutation are at high lifetime risk of breast cancer, but there is no consensus regarding an effective and safe chemoprevention strategy. A large body of evidence suggests that 3,3-diindolylmethane (DIM), a dimer of indole-3-carbinol found in cruciferous vegetables, can potentially prevent carc...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgaa050

    authors: Yerushalmi R,Bargil S,Ber Y,Ozlavo R,Sivan T,Rapson Y,Pomerantz A,Tsoref D,Sharon E,Caspi O,Grubsrein A,Margel D

    更新日期:2020-10-15 00:00:00

  • E6AP goes viral: the role of E6AP in viral- and non-viral-related cancers.

    abstract::Since its discovery, the E3 ubiquitin ligase E6-associated protein (E6AP) has been studied extensively in two pathological contexts: infection by the human papillomavirus (HPV), and the neurodevelopmental disorder, Angelman syndrome. Vital biological links between E6AP and other viruses, namely hepatitis C virus and e...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgz072

    authors: Bandilovska I,Keam SP,Gamell C,Machicado C,Haupt S,Haupt Y

    更新日期:2019-07-06 00:00:00

  • Induction of hepatic heme oxygenase-1 and ferritin in rats by cancer chemopreventive dithiolethiones.

    abstract::Treatment of rats with the cancer chemopreventive agent 1,2-dithiole-3-thione (D3T) resulted in a significant increase in hepatic heme oxygenase (HO) activity, which corresponded to increased protein levels of HO-1. Upon further analysis of proteins related to heme metabolism, the level of ferritin, the major iron sto...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.11.2291

    authors: Primiano T,Kensler TW,Kuppusamy P,Zweier JL,Sutter TR

    更新日期:1996-11-01 00:00:00

  • Metabolism of benzo[a]pyrene by cultured human hepatocytes from multiple donors.

    abstract::Primary hepatocyte cultures from six human donors were established and their abilities to metabolize the polycyclic aromatic hydrocarbon carcinogen benzo[a]pyrene (B[a]P) were examined. Cells from each donor were plated at similar densities (1 X 10(7) cells/100 mm dish). All cultures metabolized B[a]P to a significant...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/5.12.1577

    authors: Moore CJ,Gould MN

    更新日期:1984-12-01 00:00:00

  • Generation of S phase-dependent DNA double-strand breaks by Cr(VI) exposure: involvement of ATM in Cr(VI) induction of gamma-H2AX.

    abstract::Certain hexavalent chromium [Cr(VI)] compounds are implicated as occupational respiratory carcinogens. Cr(VI) induces a broad spectrum of DNA damage, but Cr(VI)-induced DNA double-strand breaks (DSBs) have not been reported. Previously we found that Cr(VI) activates the ataxia telangiectasia mutated (ATM) kinase. ATM ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgh242

    authors: Ha L,Ceryak S,Patierno SR

    更新日期:2004-11-01 00:00:00

  • Vitamin D resistance and colon cancer prevention.

    abstract::Observational studies have been largely consistent in showing an inverse association between vitamin D and an individual's risk of developing colorectal cancer. Vitamin D protection is further supported by a range of preclinical colon cancer models, including carcinogen, genetic and dietary models. A large number of m...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgr301

    authors: Giardina C,Madigan JP,Tierney CA,Brenner BM,Rosenberg DW

    更新日期:2012-03-01 00:00:00

  • Detection of N2,3-ethanoguanine in DNA after treatment with chloroacetaldehyde in vitro.

    abstract::The reaction of chloroacetaldehyde, a reactive metabolic of the carcinogen vinyl chloride, with DNA produces in addition to the hitherto known adducts, 1,N6-ethenoadenine and 3,N4-ethenocytosine, an ethenoguanine adduct, namely N2,3-ethenoguanine. This adduct is formed in the reaction of chloroacetaldehyde with the fr...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.6.663

    authors: Oesch F,Doerjer G

    更新日期:1982-01-01 00:00:00

  • Relationship between the depletion of O6-methylguanine-DNA methyltransferase by O6-methylguanine and the stimulation of DNA synthesis and growth of cultured chick hepatocytes.

    abstract::O6-Methylguanine-DNA methyltransferase (O6-MT) has been described as a DNA repair enzyme that reverses alkylation damage at the O6 position of guanine in DNA. We demonstrate that the concentration of this protein decreases immediately prior to DNA synthesis in cultured chick hepatocytes. If intracellular levels are ex...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/13.1.33

    authors: Dutta-Choudhury TA,Couri D,Stephens RE

    更新日期:1992-01-01 00:00:00

  • Low zinc intake suppressed N-methyl-N-nitrosourea-induced mammary tumorigenesis in Sprague-Dawley rats.

    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

    authors: Lee S,Simpson M,Nimmo M,Xu Z

    更新日期:2004-10-01 00:00:00

  • Studies on the mechanism by which a tumor promoter inhibits binding of epidermal growth factor to cellular receptors.

    abstract::This study analyzes the mechanism by which the tumor promoter 12-0-tetradecanoyl-phorbol 13-acetate (TPA) inhibits binding of epidermal growth factor (EGF) to its membrane receptors in HeLa cells. Kinetic studies indicate that inhibition of EGF binding occurs within a few minutes after exposure of cells to TPA; delaye...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/1.8.669

    authors: Lee LS,Weinstein IB

    更新日期:1980-08-01 00:00:00

  • Dose-related differences in DNA adduct levels in rodent tissues following skin application of complex mixtures from air pollution sources.

    abstract::Dose-related differences in the binding of DNA reactive intermediates for three environmentally important complex mixture particulate extracts and a well-studied carcinogen, benzo[a]pyrene (BaP), were examined in female C-57 mice following multiple topical treatments ranging from 1 to 120 mg/mouse. Particulate extract...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.1.63

    authors: Gallagher JE,Jackson MA,George MH,Lewtas J

    更新日期:1990-01-01 00:00:00