Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context.

Abstract:

:Chemoprotective phytochemicals exhibit multiple activities and interact with several cellular receptors, including the aryl hydrocarbon (Ah) receptor (AhR). In this study we investigated the AhR agonist/antagonist activities of the following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin. We also investigated the AhR-dependent activities of cantharidin and emodin (in herbal extracts) in Ah-responsive MCF-7 human breast cells, HepG2 human liver cancer cells, and mouse Hepa-1 cells transiently or stably transfected with plasmids expressing a luciferase reporter gene linked to multiple copies of a consensus dioxin-responsive element. The AhR agonist activities of the compounds (1 and 10 micro M) were as high as 25% of the maximal response induced by 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and their potencies were dependent on cell context. Galangin, genistein, daidzein, and diosmin were active only in Hepa-1 cells, and cantharidin induced activity only in human HepG2 and MCF-7 cells. Western blot analysis confirmed that baicalein and emodin also induced CYP1A1 protein in the human cancer cell lines. The AhR antagonist activities of four compounds inactive as agonists in MCF-7 and HepG2 cells (kaempferol, quercetin, myricetin, and luteolin) were also investigated. Luteolin was an AhR antagonist in both cell lines, and the inhibitory effects of the other compound were dependent on cell context. These data suggest that dietary phytochemicals exhibit substantial cell context-dependent AhR agonist as well as antagonist activities. Moreover, because phytochemicals and other AhR-active compounds in food are present in the diet at relatively high concentrations, risk assessment of dietary toxic equivalents of TCDD and related compounds should also take into account AhR agonist/antagonist activities of phytochemicals.

authors

Zhang S,Qin C,Safe SH

doi

10.1289/ehp.6322

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

1877-82

issue

16

eissn

0091-6765

issn

1552-9924

journal_volume

111

pub_type

杂志文章
  • Hexavalent chromium Cr(VI) up-regulates COX-2 expression through an NFκB/c-Jun/AP-1-dependent pathway.

    abstract:BACKGROUND:Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation. However, the molecular mechanisms by which Cr(VI) causes cancers are not well understood. OBJECTIVES:We evaluated cyclooxygenase-2 (COX-2) expression and the signaling pathway leading to this induction due to Cr(VI) exposure in...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1104179

    authors: Zuo Z,Cai T,Li J,Zhang D,Yu Y,Huang C

    更新日期:2012-04-01 00:00:00

  • Pesticide use in agriculture.

    abstract::During the last three decades, the use of modern organic synthetic pesticides has increased about 40-fold. Total U.S. production, for domestic and expert use, in 1976 was about 1.4 million pounds. Crops receiving the most intensive application of various pesticides were cotton for insecticides, corn for herbicides, an...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7827103

    authors: Ridgway RL,Tinney JC,MacGregor JT,Starler NJ

    更新日期:1978-12-01 00:00:00

  • An approach to the development of quantitative models to assess the effects of exposure to environmentally relevant levels of endocrine disruptors on homeostasis in adults.

    abstract::The workshop "Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels" was held to provide a forum for discussions and recommendations of methods and data needed to improve risk assessments of endocrine disruptors. This article was produced by a working group charged with de...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.99107s4605

    authors: Ben-Jonathan N,Cooper RL,Foster P,Hughes CL,Hoyer PB,Klotz D,Kohn M,Lamb DJ,Stancel GM

    更新日期:1999-08-01 00:00:00

  • Monitoring breast milk contamination to detect hazards from waste disposal.

    abstract::Human milk is a repository for certain classes of long-lived, fat-soluble environmental contaminant chemicals. Some members of this class, such as the chlorinated pesticides and the chlorinated biphenyls, can be expected to be present at chemical waste disposal sites. Analysis of samples of breast milk obtained from w...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.834887

    authors: Rogan W,Gladen B

    更新日期:1983-02-01 00:00:00

  • Blood pressure in relation to concentrations of PCB congeners and chlorinated pesticides.

    abstract:BACKGROUND:Residents of Anniston, Alabama, live near a Monsanto plant that manufactured polychlorinated biphenyls (PCBs) from 1929 to 1971 and are relatively heavily exposed. OBJECTIVES:The goal of this study was to determine the relationship, if any, between blood pressure and levels of total serum PCBs, several PCB ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1002830

    authors: Goncharov A,Pavuk M,Foushee HR,Carpenter DO,Anniston Environmental Health Reseach Consortium.

    更新日期:2011-03-01 00:00:00

  • Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

    abstract::Polychlorinated biphenyls (PCBs) are a family of persistent organic contaminants suspected to cause adverse effects in wildlife and humans. In rodents, PCBs bind to the aryl hydrocarbon (AhR) and pregnane X receptors (PXR) inducing the expression of catabolic cytochrome p450 enzymes of the CYP1A and 3A families. We fo...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.6560

    authors: Tabb MM,Kholodovych V,Grün F,Zhou C,Welsh WJ,Blumberg B

    更新日期:2004-02-01 00:00:00

  • Follow-up screening of lead-poisoned children near an auto battery recycling plant, Haina, Dominican Republic.

    abstract::In August 1997 we performed a follow-up survey of 146 lead-poisoned children from a community near a previously active auto battery recycling smelter in Haina near Santo Domingo, Dominican Republic. Our follow-up survey confirmed a severe incidence of elevated blood lead (BPb) and erythrocyte protoporphyrin/zinc proto...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.99107917

    authors: Kaul B,Sandhu RS,Depratt C,Reyes F

    更新日期:1999-11-01 00:00:00

  • Climate factors influencing coccidioidomycosis seasonality and outbreaks.

    abstract::Although broad links between climatic factors and coccidioidomycosis have been established, the identification of simple and robust relationships linking climatic controls to seasonal timing and outbreaks of the disease has remained elusive. Using an adaptive data-oriented method for estimating date of exposure, in th...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7786

    authors: Comrie AC

    更新日期:2005-06-01 00:00:00

  • Genetic and molecular ecotoxicology: a research framework.

    abstract::Participants at the Napa Conference on Genetic and Molecular Ecotoxicology assessed the status of this field in light of heightened concerns about the genetic effects of exposure to hazardous substances and recent advancements in our capabilities to measure those effects. We present here a synthesis of the ideas discu...

    journal_title:Environmental health perspectives

    pub_type: 共识发展会议,杂志文章,评审

    doi:10.1289/ehp.94102s123

    authors: Anderson S,Sadinski W,Shugart L,Brussard P,Depledge M,Ford T,Hose J,Stegeman J,Suk W,Wirgin I

    更新日期:1994-12-01 00:00:00

  • Acute exposure to environmental tobacco smoke and heart rate variability.

    abstract::Environmental tobacco smoke (ETS) has been associated with cardiovascular mortality. Pathophysiologic pathways leading from ETS exposure to cardiopulmonary disease are still being explored. Reduced cardiac autonomic function, as measured by heart rate variability (HRV), has been associated with cardiac vulnerability a...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.01109711

    authors: Pope CA 3rd,Eatough DJ,Gold DR,Pang Y,Nielsen KR,Nath P,Verrier RL,Kanner RE

    更新日期:2001-07-01 00:00:00

  • Use of selected toxicology information resources in assessing relationships between chemical structure and biological activity.

    abstract::This paper addresses the subject of the use of selected toxicology information resources in assessing relationships between chemical structure and specific biological end points. To assist the researcher in how to access the primary literature of genetic toxicology, teratogenesis, and carcinogenesis, three specific sp...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.8561287

    authors: Wassom JS

    更新日期:1985-09-01 00:00:00

  • Tetrahydrofurandiol stimulation of phospholipase A2, lipoxygenase, and cyclooxygenase gene expression and MCF-7 human breast cancer cell proliferation.

    abstract:BACKGROUND:We characterized an endocrine disruptor from ground corncob bedding material that interferes with male and female sexual behavior and ovarian cyclicity in rats and stimulates estrogen receptor (ER)-positive and ER-negative breast cancer cell proliferation. The agents were identified as an isomeric mixture of...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.10659

    authors: Markaverich BM,Crowley J,Rodriquez M,Shoulars K,Thompson T

    更新日期:2007-12-01 00:00:00

  • Respiratory involvement and immune status in yusho patients.

    abstract::Clinical and experimental studies on respiratory involvement and alterations in immune status were carried out. Respiratory distress occurring in these patients has improved gradually for 14 years but still remains. Copious expectoration at an early stage of the disease may be related to the fact that a number of disc...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.59-1568074

    authors: Nakanishi Y,Shigematsu N,Kurita Y,Matsuba K,Kanegae H,Ishimaru S,Kawazoe Y

    更新日期:1985-02-01 00:00:00

  • Chromium(VI) reduction by ascorbate: role of reactive intermediates in DNA damage in vitro.

    abstract::Reaction of chromium(VI) with one equivalent of ascorbate was studied by electron paramagnetic resonance spectroscopy in the presence of 0.10 M 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) at room temperature in 0.10 M (N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]) (HEPES) and 0.05 M tris(hydroxymethyl)aminometh...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.94102s321

    authors: Stearns DM,Courtney KD,Giangrande PH,Phieffer LS,Wetterhahn KE

    更新日期:1994-09-01 00:00:00

  • Interaction between environmental pollutants and respiratory infections.

    abstract::The major aspects that must be considered in studies of the health effects of environmental pollutants are: the direct damage due to the exposure, the role of pre-existing disease, and effects of the exposure on the response to secondary stresses. In experimental studies at concentrations of air pollutants found in ur...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.803589

    authors: Ehrlich R

    更新日期:1980-04-01 00:00:00

  • Household air pollution from coal and biomass fuels in China: measurements, health impacts, and interventions.

    abstract:OBJECTIVE:Nearly all China's rural residents and a shrinking fraction of urban residents use solid fuels (biomass and coal) for household cooking and/or heating. Consequently, global meta-analyses of epidemiologic studies indicate that indoor air pollution from solid fuel use in China is responsible for approximately 4...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.9479

    authors: Zhang JJ,Smith KR

    更新日期:2007-06-01 00:00:00

  • A cross-sectional investigation of chronic exposure to microcystin in relationship to childhood liver damage in the Three Gorges Reservoir Region, China.

    abstract:BACKGROUND:Microcystin-producing Microcystis bloom is a severe water problem in the world. Some reports indicate that chronic exposure to microcystin may result in liver damage in adults, but information on effects in children is limited. OBJECTIVE:We investigated the relationship between microcystin exposure and live...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1002412

    authors: Li Y,Chen JA,Zhao Q,Pu C,Qiu Z,Zhang R,Shu W

    更新日期:2011-10-01 00:00:00

  • The World Trade Center residents' respiratory health study: new-onset respiratory symptoms and pulmonary function.

    abstract::The destruction of the World Trade Center (WTC) on 11 September 2001 in New York City resulted in the massive release of pulverized dust and combustion products. The dust and smoke settled in the surrounding area, which encompassed a large residential community. We hypothesized that previously normal residents in the ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7375

    authors: Reibman J,Lin S,Hwang SA,Gulati M,Bowers JA,Rogers L,Berger KI,Hoerning A,Gomez M,Fitzgerald EF

    更新日期:2005-04-01 00:00:00

  • The developing brain and the environment: an introduction.

    abstract::mental retardation: timing and thresholds; (italic)b(/italic)) endocrine dysfunction and developmental disabilities: dose and target implications; (italic)c(/italic)) attention-deficit disorder-ADHD and learning disabilities; and (italic)d(/italic)) new horizons: extending the boundaries. Support for the Rochester con...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.00108s3373

    authors: Weiss B,Landrigan PJ

    更新日期:2000-06-01 00:00:00

  • Detection of lipocortin 1 in human lung lavage fluid: lipocortin degradation as a possible proteolytic mechanism in the control of inflammatory mediators and inflammation.

    abstract::Lipocortins are structurally related, glucocorticoid-inducible proteins that inhibit phospholipase A2 (PLA2), thereby reducing the liberation of arachidonic acid from phospholipids and so limiting the synthesis of eicosanoid inflammatory mediators. This study is the first demonstration of one lipocortin, lipocortin 1 ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.85-1568329

    authors: Smith SF,Tetley TD,Guz A,Flower RJ

    更新日期:1990-04-01 00:00:00

  • Hypersensitivity pneumonitis from ordinary residential exposures.

    abstract::A previously healthy woman developed hypersensitivity pneumonitis of such severity that she required chronic systemic corticosteroid therapy for symptom control. Detailed investigation of her workplace and home environments revealed fungi in her typical suburban home, to which she had specific serum precipitating anti...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.01109979

    authors: Apostolakos MJ,Rossmoore H,Beckett WS

    更新日期:2001-09-01 00:00:00

  • Chromosomal methods in population studies.

    abstract::A brief description of chromosome aberrations and sister chromatid exchange (SCE) as cytogenetic endpoints for evaluation of DNA damaging agents is presented. Problems associated with the use of cytogenetic assays as population monitors of radiation and chemical exposures are discussed. Adequate cell sample size requi...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.8142107

    authors: Conner MK,Wald N

    更新日期:1981-12-01 00:00:00

  • Significance of high soil lead concentrations for childhood lead burdens.

    abstract::The lead exposure of children and their mothers has been studied in two towns with mean soil lead contents of 900 and 400 ppm. No significant difference in blood or fecal lead contents was demonstrated between the two populations, but a small difference in hair lead content was shown. The blood lead content of childre...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.74775

    authors: Barltrop D,Strehlow CD,Thorton I,Webb JS

    更新日期:1974-05-01 00:00:00

  • Calcium in renal cells. Modulation of calcium-dependent activation of phospholipase A2.

    abstract::Calcium has been implicated as a regulatory factor in many physiological and pathophysiological processes in the renal cell. Under physiological conditions, the cytosolic free calcium concentration is maintained at approximately 100 nM. Most of the releasable cell Ca2+ resides in the nonmitochondrial compartments. In ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.9084155

    authors: Bonventre JV

    更新日期:1990-03-01 00:00:00

  • State monitoring activities related to Pfiesteria-like organisms.

    abstract::In response to potential threats to human health and fish populations, six states along the east coast of the United States initiated monitoring programs related to Pfiesteria-like organisms in 1998. These actions were taken in the wake of toxic outbreaks of Pfiesteria piscicida Steidinger & Burkholder in Maryland dur...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.01109s5711

    authors: Magnien RE

    更新日期:2001-10-01 00:00:00

  • Litigation-generated science: why should we care?

    abstract:BACKGROUND:In a 1994 Ninth Circuit decision on the remand of Daubert v. Merrell Dow Pharmaceuticals, Inc., Judge Alex Kosinski wrote that science done for the purpose of litigation should be subject to more stringent standards of admissibility than other science. OBJECTIVES:We analyze this proposition by considering l...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.9987

    authors: Boden LI,Ozonoff D

    更新日期:2008-01-01 00:00:00

  • Estimating Time-Varying PCB Exposures Using Person-Specific Predictions to Supplement Measured Values: A Comparison of Observed and Predicted Values in Two Cohorts of Norwegian Women.

    abstract:BACKGROUND:Studies on the health effects of polychlorinated biphenyls (PCBs) call for an understanding of past and present human exposure. Time-resolved mechanistic models may supplement information on concentrations in individuals obtained from measurements and/or statistical approaches if they can be shown to reprodu...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1409191

    authors: Nøst TH,Breivik K,Wania F,Rylander C,Odland JØ,Sandanger TM

    更新日期:2016-03-01 00:00:00

  • The U.S. EPA Conference on Preventable Causes of Cancer in Children: a research agenda.

    abstract::On 15-16 September 1997, the U.S. Environmental Protection Agency sponsored the Conference on Preventable Causes of Cancer in Children. The conference was convened to examine rising trends in reported incidence of childhood cancer and the association of these trends with environmental exposures. This paper summarizes ...

    journal_title:Environmental health perspectives

    pub_type:

    doi:10.1289/ehp.98106867

    authors: Carroquino MJ,Galson SK,Licht J,Amler RW,Perera FP,Claxton LD,Landrigan PJ

    更新日期:1998-06-01 00:00:00

  • Evaluation of the effectiveness of mass screening for uterine cancer in Japan: the potential years of life lost.

    abstract::To evaluate the effectiveness of mass screening for uterine cancer in Japan, we compared the changes in the age-adjusted rates of potential years of life lost (PYLL) due to uterine cancer between 1969 and 1972 to 1973 through 1977 between the high coverage-rate (intensively screened) areas and the comparable control a...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.908751

    authors: Kuroishi T,Hirose K,Tominaga S

    更新日期:1990-07-01 00:00:00

  • Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research.

    abstract:BACKGROUND:The National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may prese...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/EHP5133

    authors: Pellizzari ED,Woodruff TJ,Boyles RR,Kannan K,Beamer PI,Buckley JP,Wang A,Zhu Y,Bennett DH,(Environmental influences on Child Health Outcomes).

    更新日期:2019-12-01 00:00:00