Aromatic hydrocarbon receptor polymorphism: development of new methods to correlate genotype with phenotype.


:Differential CYP1A1 inducibility, reflecting variations in aromatic hydrocarbon receptor (AHR) affinity among inbred mouse strains, is an important determinant of environmental toxicity. We took advantage of the Ahr polymorphism in C57BL/6 and DBA/2 mice to develop an oligonucleotide-hybridization screening approach for the rapid identification of DNA sequence differences between Ahr alleles. Oligonucleotides containing single-base changes at polymorphic sites were immobilized on a solid support and hybridized with C57BL/6 or DBA/2 AHR cDNA radiolabeled probes. The observed hybridization patterns demonstrate that this approach can be used to detect nucleotide differences in the Ahr coding region with very high accuracy. In parallel experiments, we used a yeast two-hybrid system to assess phenotypic differences in AHR function. AHR activation, as measured by beta-galactosidase reporter activity in Saccharomyces cerevisiae strain SFY526, was determined following treatment with varying doses of the AHR ligand beta-naphthoflavone (BNF). We found that the C57BL/6 AHR has about a 15-fold higher affinity for BNF than the DBA/2 AHR, in much better agreement with results reported for whole-animal studies than the values observed by in vitro ligand-binding assays. Using C57BL/6 and DBA/2 AHR chimeric proteins, we also confirmed the previously reported observation that an A375V change is principally responsible for the high- to low-affinity AHR phenotype. There has been no straightforward method to reliably and reproducibly phenotype large numbers of humans for CYP1A1 inducibility or AHR affinity. Screening human AHR cDNAs by oligonucleotide-hybridization and yeast two-hybrid methodologies will be invaluable for the rapid and unequivocal determination of changes in DNA sequence and receptor-ligand affinities associated with human AHR polymorphisms.


Maier A,Micka J,Miller K,Denko T,Chang CY,Nebert DW,Alvaro Puga




Has Abstract


1998-07-01 00:00:00












  • Accelerated mammary tumor onset in a HER2/Neu mouse model exposed to DDT metabolites locally delivered to the mammary gland.

    abstract:BACKGROUND:The association of DDT (dichlorodiphenyltrichloroethane) with breast cancer is controversial, but animal studies directly linking DDT to risk are lacking. Concerns with DDT reside in its environmental persistence, bioaccumulation in breast adipose tissue, and endocrine-disrupting actions. Whereas most attent...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Johnson NA,Ho A,Cline JM,Hughes CL,Foster WG,Davis VL

    更新日期:2012-08-01 00:00:00

  • Caring for medically unexplained physical symptoms after toxic environmental exposures: effects of contested causation.

    abstract::Medically unexplained physical symptoms (MUPS) are persistent idiopathic symptoms that drive patients to seek medical care. MUPS syndromes include chronic fatigue syndrome, fibromyalgia syndrome, and multiple chemical sensitivities. When MUPS occur after an environmental exposure or injury, an adversarial social conte...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审


    authors: Engel CC Jr,Adkins JA,Cowan DN

    更新日期:2002-08-01 00:00:00

  • Effect of water temperature on dermal exposure to chloroform.

    abstract::We have developed and applied a new measurement methodology to investigate dermal absorption of chloroform while bathing. Ten subjects bathed in chlorinated water while breathing pure air through a face mask. Their exhaled breath was delivered to a glow discharge source/ion trap mass spectrometer for continuous real-t...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Gordon SM,Wallace LA,Callahan PJ,Kenny DV,Brinkman MC

    更新日期:1998-06-01 00:00:00

  • Effects of lead on the kidney: roles of high-affinity lead-binding proteins.

    abstract::Lead-induced nephropathy produces both tubular and interstitial manifestations of cell injury, but the pathophysiology of these lesions is not completely understood. Delineation of the molecular factors underlying renal handling of lead is one of central importance in understanding the mechanisms of renal cell injury ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Fowler BA,DuVal G

    更新日期:1991-02-01 00:00:00

  • Association of genetic polymorphisms in CYP2E1, MPO, NQO1, GSTM1, and GSTT1 genes with benzene poisoning.

    abstract::Metabolic enzymes involved in benzene activation or detoxification, including NAD(P)H, quinone oxidoreductase 1 (NQO1), cytochrome P450 2E1 (CYP2E1), myeloperoxidase (MPO), glutathione-S-transferase mu-1 (GSTM1), and glutathione-S-transferase theta-1 (GSTT1), were studied for their roles in human susceptibility to ben...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Wan J,Shi J,Hui L,Wu D,Jin X,Zhao N,Huang W,Xia Z,Hu G

    更新日期:2002-12-01 00:00:00

  • Testing their metal.

    abstract::Metals continually rank at the top of the U.S. Environmental Protection Agency's annual list of agents that pose the greatest hazard to the people of the United States. Metals aren't going away, either. They do not biodegrade, and they often concentrate in human and animal cells and tissue. Many metals are known human...

    journal_title:Environmental health perspectives

    pub_type: 新闻


    authors: Fisher BE

    更新日期:1999-05-01 00:00:00

  • Efficient elimination of inhaled nanoparticles from the alveolar region: evidence for interstitial uptake and subsequent reentrainment onto airways epithelium.

    abstract:BACKGROUND:There is ongoing discussion that inhaled nanoparticles (NPs, < 100 nm) may translocate from epithelial deposition sites of the lungs to systemic circulation. OBJECTIVES AND METHODS:We studied the disappearance of NPs from the epithelium by sequential lung retention and clearance and bronchoalveolar lavage (...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Semmler-Behnke M,Takenaka S,Fertsch S,Wenk A,Seitz J,Mayer P,Oberdörster G,Kreyling WG

    更新日期:2007-05-01 00:00:00

  • Review of methods applicable to the assessment of mold exposure to children.

    abstract::This article presents discussion of the assessment of the exposure of children to fungi, substances derived from fungi, and the environmental conditions that may lead to exposure. The principles driving investigations of fungal contamination and subsequent exposure are presented as well as guidelines for conducting th...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审


    authors: Dillon HK,Miller JD,Sorenson WG,Douwes J,Jacobs RR

    更新日期:1999-06-01 00:00:00

  • Prevalence and determinants of lead intoxication in Mexican children of low socioeconomic status.

    abstract::This paper reports on the prevalence of lead poisoning in children between 1 and 5 years of age living in a marginal area to the north of Mexico City and also includes an evaluation of sources of exposure to this metal in the same area. The results show that 67.5% of the children studied have blood lead (PbB) levels >...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: López-Carrillo L,Torres-Sánchez L,Garrido F,Papaqui-Hernández J,Palazuelos-Rendón E,López-Cervantes M

    更新日期:1996-11-01 00:00:00

  • Human colon microbiota transform polycyclic aromatic hydrocarbons to estrogenic metabolites.

    abstract::Ingestion is an important exposure route for polycyclic aromatic hydrocarbons (PAHs) to enter the human body. Although the formation of hazardous PAH metabolites by human biotransformation enzymes is well documented, nothing is known about the PAH transformation potency of human intestinal microbiota. Using a gastroin...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Van de Wiele T,Vanhaecke L,Boeckaert C,Peru K,Headley J,Verstraete W,Siciliano S

    更新日期:2005-01-01 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


    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

  • Predicting children's short-term exposure to pesticides: results of a questionnaire screening approach.

    abstract::The ability of questionnaires to predict children's exposure to pesticides was examined as part of the Minnesota Children's Pesticide Exposure Study (MNCPES). The MNCPES focused on a probability sample of 102 children between the ages of 3 and 13 years living in either urban (Minneapolis and St. Paul, MN) or nonurban ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Sexton K,Adgate JL,Eberly LE,Clayton CA,Whitmore RW,Pellizzari ED,Lioy PJ,Quackenboss JJ

    更新日期:2003-01-01 00:00:00

  • Developmental toxicity of ethylene glycol monopropyl ether acetate (EGPEA) in the rat.

    abstract::Pregnant rats were exposed by inhalation to vapor concentrations of 100, 200, 400 or 800 ppm of ethylene glycol monopropyl ether acetate on days 6 through 15 of gestation. Concentrations of 400 and 800 ppm reduced the feed intake, mean body weight and red blood cell counts. Mean corpuscular volume and mean corpuscular...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Krasavage WJ,Katz GV

    更新日期:1984-08-01 00:00:00

  • Detection of genetic effects of environmental agents.

    abstract::The fundamental problems in population monitoring for genetic effects are twofold: the binomialized nature of the data and the lower power due to small risk of finding positive results. The binomial character is artificial, even forced, and can with advantage be replaced by more refined analysis, and by a focus on all...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Murphy EA

    更新日期:1981-12-01 00:00:00

  • Relationships among polycyclic aromatic hydrocarbon-DNA adducts, proximity to the World Trade Center, and effects on fetal growth.

    abstract::Polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants released by the World Trade Center (WTC) fires and various urban combustion sources. Benzo[a]pyrene (BaP) is a representative member of the class of PAHs. PAH-DNA adducts, or BaP-DNA adducts as their proxy, provide a measure of chemical-specific genetic dama...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Perera FP,Tang D,Rauh V,Lester K,Tsai WY,Tu YH,Weiss L,Hoepner L,King J,Del Priore G,Lederman SA

    更新日期:2005-08-01 00:00:00

  • Identifying environmental factors harmful to reproduction.

    abstract::Reproduction is essential for the continuation of the species and for life itself. In biological terms, living and reproducing are essentially one and the same. There is, therefore, no sharp division between identifying factors harmful to reproduction and identifying factors harmful to life or vice versa. Detection of...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Palmer AK

    更新日期:1993-07-01 00:00:00

  • The Salmonella mutagenicity assay: the stethoscope of genetic toxicology for the 21st century.

    abstract:OBJECTIVES:According to the 2007 National Research Council report Toxicology for the Twenty-First Century, modern methods (e.g., "omics," in vitro assays, high-throughput testing, computational methods) will lead to the emergence of a new approach to toxicology. The Salmonella mammalian microsome mutagenicity assay has...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审


    authors: Claxton LD,Umbuzeiro Gde A,DeMarini DM

    更新日期:2010-11-01 00:00:00

  • An experimental approach to the evaluation of the biopersistence of respirable synthetic fibers and minerals.

    abstract::The biopersistence of fibers and minerals in the respiratory tract is an important parameter in the toxicity of those materials. The biopersistence of respirable synthetic fibers and minerals in man can be most closely evaluated in an animal model. While acellular and in vitro systems are important for initial evaluat...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Bernstein DM,Mast R,Anderson R,Hesterberg TW,Musselman R,Kamstrup O,Hadley J

    更新日期:1994-10-01 00:00:00

  • Cumulative dietary energy intake determines the onset of puberty in female rats.

    abstract::Laboratory animal diets for studies to determine the endocrine-disrupting potential of chemicals are under scrutiny because they can affect both assay control values and assay sensitivity. Although phytoestrogen content is important, we have previously shown that a phytoestrogen-rich diet and a phytoestrogen-free diet...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Odum J,Tinwell H,Tobin G,Ashby J

    更新日期:2004-11-01 00:00:00

  • Setting a new syllabus: environmental health science in the classroom.

    abstract::Environmental health is a subject that has only relatively recently become prominent in the social consciousness. Even as its significance becomes known, finding ways to integrate the subject into education for primary and secondary students is difficult because of federal testing requirements under the No Child Left ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Brown VJ

    更新日期:2004-10-01 00:00:00

  • Chemical-biological reactions common to teratogenesis and mutagenesis.

    abstract::Cytotoxic chemicals have in common the ability to act specifically on cells in cycle. Bacteria are more sensitive in the exponential growth phase than when growing slowly in media. Similar observations have been made on a variety of systems ranging from bacteria, yeast, higher plants and invertebrates to vertebrates i...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Harbison RD

    更新日期:1978-06-01 00:00:00

  • Risks and benefits of green spaces for children: a cross-sectional study of associations with sedentary behavior, obesity, asthma, and allergy.

    abstract:BACKGROUND:Green spaces have been associated with both health benefits and risks in children; however, available evidence simultaneously investigating these conflicting influences, especially in association with different types of greenness, is scarce. OBJECTIVES:We aimed to simultaneously evaluate health benefits and...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Dadvand P,Villanueva CM,Font-Ribera L,Martinez D,Basagaña X,Belmonte J,Vrijheid M,Gražulevičienė R,Kogevinas M,Nieuwenhuijsen MJ

    更新日期:2014-12-01 00:00:00

  • Metabolism of 2-aminofluorene by human polymorphonuclear leukocytes: more evidence for the association between inflammation and cancer.

    abstract::Recent investigations have demonstrated the ability of leukocytes to metabolize promutagens or procarcinogens into their genotoxic forms. As a possible explanation for the association between inflammation and cancer, we and others have hypothesized that local accumulations of leukocytes could take up nearby promutagen...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Isola VJ,Hartman TC,Trumble SJ,Ruzek MC,Gentile JM

    更新日期:1993-10-01 00:00:00

  • Assessing potential health risks from microcystin toxins in blue-green algae dietary supplements.

    abstract::The presence of blue-green algae (BGA) toxins in surface waters used for drinking water sources and recreation is receiving increasing attention around the world as a public health concern. However, potential risks from exposure to these toxins in contaminated health food products that contain BGA have been largely ig...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Gilroy DJ,Kauffman KW,Hall RA,Huang X,Chu FS

    更新日期:2000-05-01 00:00:00

  • Personal exposure to ultrafine particles and oxidative DNA damage.

    abstract::Exposure to ultrafine particles (UFPs) from vehicle exhaust has been related to risk of cardiovascular and pulmonary disease and cancer, even though exposure assessment is difficult. We studied personal exposure in terms of number concentrations of UFPs in the breathing zone, using portable instruments in six 18-hr pe...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Vinzents PS,Møller P,Sørensen M,Knudsen LE,Hertel O,Jensen FP,Schibye B,Loft S

    更新日期:2005-11-01 00:00:00

  • Health advisories for consumers of Great Lakes sport fish: is the message being received?

    abstract::Nationwide, 45 states issue health advisories for sport fish consumers. Chemical contaminants in some Great Lakes (GL) sport fish include compounds suspected of causing adverse reproductive and developmental effects. Although advisories to reduce consumption of contaminated fish, especially by women, have been issued ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Tilden J,Hanrahan LP,Anderson H,Palit C,Olson J,Kenzie WM

    更新日期:1997-12-01 00:00:00

  • Application of HPLC to the isolation of molecular targets in dosimetry studies.

    abstract::High-performance liquid chromatography (HPLC) methods are described which permit the rapid isolation of multiple target macromolecules from the tissues of animals exposed to chemical mutagens. DNA and selected chromosomal proteins are isolated in a simple two step separation scheme. Isolated nuclei are dissolved in 3 ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Balhorn R,Mazrimas JA,Corzett M

    更新日期:1985-10-01 00:00:00

  • May 2006 NEIHS News.

    abstract::Short articles on the following topics: *NIEHS Strategic Plan: New Frontiers in Environmental Sciences and Human Health; Beyond the Bench: Environmental Health Nursing: Putting Knowledge into Practice; Headliners: Inhibition of RLIP76 Causes Complete Regression of Melanoma in Mice. ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Hood E,Tillett T,Phelps J

    更新日期:2006-05-01 00:00:00

  • Developmental exposure to PCBs, MeHg, or both: long-term effects on auditory function.

    abstract:BACKGROUND:Developmental exposure to polychlorinated biphenyls (PCBs) or methylmercury (MeHg) can result in a variety of neurotoxic effects, including long-term auditory deficits. However, little is known about the effects of combined exposure to PCBs and MeHg on auditory function. OBJECTIVE:We developmentally exposed...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Powers BE,Poon E,Sable HJ,Schantz SL

    更新日期:2009-07-01 00:00:00

  • Estimated reduction in cancer risk due to PAH exposures if source control measures during the 2008 Beijing Olympics were sustained.

    abstract:BACKGROUND:The 2008 Beijing Olympic Games provided a unique case study to investigate the effect of source control measures on the reduction in air pollution, and associated inhalation cancer risk, in a Chinese megacity. OBJECTIVES:We measured 17 carcinogenic polycyclic aromatic hydrocarbons (PAHs) and estimated the l...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章


    authors: Jia Y,Stone D,Wang W,Schrlau J,Tao S,Simonich SL

    更新日期:2011-06-01 00:00:00