Roles of CYP1 & 19 in Fundulus Steroids & PAH Metabolism
CYP1 的作用
基本信息
- 批准号:7909572
- 负责人:
- 金额:$ 8.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-06 至 2010-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAnimal ModelAromataseAromatic Polycyclic HydrocarbonsBenzo(a)pyreneBiologicalBiological MonitoringCYP19A1 geneCancer ModelChorionCytochrome P450CytochromesDNA AdductionDNA AdductsDevelopmentEndocrine disruptionEpoxy CompoundsEstrogen MetabolismEstrogensFishesFundulusFundulus heteroclitusGenesHealthHumanHuman DevelopmentIn VitroMalignant NeoplasmsMammalsMeasuresMediatingMetabolicMetabolismModelingMolecularOxidation-ReductionOxidative StressPredispositionProductionRecombinantsResearchResearch PersonnelRoleSpecificitySteroidsSystemTestingTherapeuticTissuesToxic effectToxicologyTumor TissueVertebratesegggenotoxicityin vivopollutantprogramsreproductivereproductive successsteroid metabolismsuccesstumor
项目摘要
DESCRIPTION (provided by applicant): Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are a human health concern because they are implicated in human cancers and endocrine disruption. The fish Fundulus heteroclitus will be used as a model organism to investigate the central hypothesis that CYP1B and/or CYP19 are involved in the molecular mechanisms of benzo(a)pyrene-mediated toxicity. The Specific Aims are to:
1) Assess the respective roles of CYP1B and CYP19s in BaP and estrogen metabolism and estrogen synthesis with in vitro recombinant systems,
2) Determine the extent, to which BaP-induced CYP1 B-mediated metabolism is important in genotoxicity. Aim 2.1: In adult fish following BaP exposure, the relationship between tissue specific CYP1B expression, toxic metabolite formation, DNA adducts and oxidative stress will be quantitated. Aim 2.2: Determine how egg or larval BaP-exposure affects CYP1B expression and associated toxicological endpoints. Aim 2.3: Determine how CYP1B and CYP19 are up-regulated in tumor tissues in exposed fish.
3) Measure the association between BaP-induced changes in aromatase and Fundulus reproductive or developmental success.
Aim 3.1: Determine if maternal BaP-exposure decreases reproductive success.
Aim 3.2: Determine if and how egg and larval BaP exposures alter aromatase expression and if this is correlated with developmental deficiencies. Successful completion of these Aims will provide a greater molecular understanding of these important P450 genes and their role in the mechanisms of action of PAHs. This research will further define the utility of Fundulus as a model organism for studying PAH-associated toxicities and in the development of human CYP19 or CYP1 B-related therapeutics.
描述(由申请人提供):多环芳烃(PAH)是普遍存在的污染物,是人类健康问题,因为它们与人类癌症和内分泌干扰有关。将以鱼类底栖动物作为模式生物,研究CYP 1B和/或CYP 19参与苯并(a)芘介导毒性的分子机制这一中心假设。具体目标是:
1)使用体外重组系统评估CYP 1B和CYP 19在BaP和雌激素代谢以及雌激素合成中的各自作用,
2)确定BaP诱导的CYP 1 B介导的代谢在遗传毒性中的重要程度。目标2.1:在BaP暴露后的成鱼中,将定量组织特异性CYP 1B表达、毒性代谢物形成、DNA加合物和氧化应激之间的关系。目的2.2:确定卵或幼虫BaP暴露如何影响CYP 1B表达和相关毒理学终点。目的2.3:确定CYP 1B和CYP 19如何在暴露鱼的肿瘤组织中上调。
3)测量苯并(a)芘诱导的芳香化酶变化与基底生殖或发育成功之间的关联。
目标3.1:确定母体苯并(a)芘暴露是否会降低生殖成功率。
目的3.2:确定卵和幼虫苯并(a)芘暴露是否以及如何改变芳香化酶表达,以及这是否与发育缺陷相关。这些目标的成功完成将为这些重要的P450基因及其在多环芳烃作用机制中的作用提供更深入的分子理解。本研究将进一步确定底作为研究PAH相关毒性和开发人CYP 19或CYP 1 B相关治疗药物的模式生物的效用。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Benzo[a]pyrene effects on glycine N-methyltransferase mRNA expression and enzyme activity in Fundulus heteroclitus embryos.
- DOI:10.1016/j.aquatox.2010.02.004
- 发表时间:2010-06-10
- 期刊:
- 影响因子:4.5
- 作者:Fang, Xiefan;Dong, Wu;Thornton, Cammi;Willett, Kristine L.
- 通讯作者:Willett, Kristine L.
Benzo(a)pyrene induced glycine N-methyltransferase messenger RNA expression in Fundulus heteroclitus embryos.
苯并(a)芘诱导异斜眼底胚胎中甘氨酸 N-甲基转移酶信使 RNA 的表达。
- DOI:10.1016/j.marenvres.2009.10.008
- 发表时间:2010
- 期刊:
- 影响因子:3.3
- 作者:Fang,Xiefan;Dong,Wu;Thornton,Cammi;Scheffler,Brian;Willett,KristineL
- 通讯作者:Willett,KristineL
Expression of CYP1C1 and CYP1A in Fundulus heteroclitus during PAH-induced carcinogenesis.
- DOI:10.1016/j.aquatox.2010.06.002
- 发表时间:2010-09
- 期刊:
- 影响因子:4.5
- 作者:Lu Wang;A. Camus;Wu Dong;C. Thornton;K. Willett
- 通讯作者:Lu Wang;A. Camus;Wu Dong;C. Thornton;K. Willett
Effects of benzo(a)pyrene exposure on killifish (Fundulus heteroclitus) aromatase activities and mRNA.
- DOI:10.1016/j.aquatox.2005.12.009
- 发表时间:2006-05
- 期刊:
- 影响因子:4.5
- 作者:Monali Patel;B. Scheffler;Lu Wang;K. Willett
- 通讯作者:Monali Patel;B. Scheffler;Lu Wang;K. Willett
Functional differences in the cytochrome P450 1 family enzymes from zebrafish (Danio rerio) using heterologously expressed proteins.
- DOI:10.1016/j.abb.2010.06.018
- 发表时间:2010-10-01
- 期刊:
- 影响因子:3.9
- 作者:Scornaienchi ML;Thornton C;Willett KL;Wilson JY
- 通讯作者:Wilson JY
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KRISTINE L WILLETT其他文献
KRISTINE L WILLETT的其他文献
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{{ truncateString('KRISTINE L WILLETT', 18)}}的其他基金
Developmental Toxicity of Cannabidiol and Δ9-Tetrahydrocannabinol
大麻二酚和α9-四氢大麻酚的发育毒性
- 批准号:
9371725 - 财政年份:2017
- 资助金额:
$ 8.62万 - 项目类别:
Development of a fish model for epigenetic & multigenerational contaminant effect
表观遗传鱼类模型的开发
- 批准号:
8319336 - 财政年份:2011
- 资助金额:
$ 8.62万 - 项目类别:
Development of a fish model for epigenetic & multigenerational contaminant effect
表观遗传鱼类模型的开发
- 批准号:
8191628 - 财政年份:2011
- 资助金额:
$ 8.62万 - 项目类别:
BaP-mediated reproductive and developmental toxicity
BaP 介导的生殖和发育毒性
- 批准号:
8061604 - 财政年份:2010
- 资助金额:
$ 8.62万 - 项目类别:
BaP-mediated reproductive and developmental toxicity
BaP 介导的生殖和发育毒性
- 批准号:
7870863 - 财政年份:2010
- 资助金额:
$ 8.62万 - 项目类别:
Roles of CYP1 & 19 in Fundulus Steroids & PAH Metabolism
CYP1 的作用
- 批准号:
7417376 - 财政年份:2004
- 资助金额:
$ 8.62万 - 项目类别:
Roles of CYP1 & 19 in Fundulus Steroids & PAH Metabolism
CYP1 的作用
- 批准号:
7226210 - 财政年份:2004
- 资助金额:
$ 8.62万 - 项目类别:
Roles of CYP1 & 19 in Fundulus Steroids & PAH Metabolism
CYP1 的作用
- 批准号:
6819825 - 财政年份:2004
- 资助金额:
$ 8.62万 - 项目类别:
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