QUANTIFYING NITROARENE GENOTOXICITY IN COMPLEX MIXTURES
QUANTIFYING NITROARENE GENOTOXICITY IN COMPLEX MIXTURES
批准号:
3252781
负责人:
HERBERT S ROSENKRANZ
金额:
$9.84万
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-08-01 至 1991-07-31
关键词:
Salmonella artificial intelligence bioassay biotransformation cancer risk chemical carcinogen chemical carcinogenesis chemical structure function engine exhaust environment related neoplasm /cancer enzyme induction /repression hamsters laboratory rat mutagen testing neoplastic cell culture for noncancer research nitrogenous heterocyclic compound tissue /cell culture toxicant screening
中文摘要
硝化多环芳烃的生物活性
碳氢化合物(硝基芳烃)已成为广泛研究的主题
主要是因为其具有强致突变性和致癌性
一些硝基芳烃以及其广泛存在于
环境,主要是由于不完全燃烧
流程. 然而,我们大多数人并不主要接触到
而是复杂的混合物,
室外(汽车、发电厂等的排放)和
室内(香烟烟雾,加热器,炉子,烤箱等)。 的
本申请中提出的工作的目的是将
个别硝基芳烃的遗传毒性和致癌活性,
排放物的人工混合物和提取物的活性
为了使用单一化学品的数据来评估
暴露于复杂混合物的风险。 拟议的项目,
它采用了计算机化和实验性的
方法,将涉及专业知识的专业人员,
化学、生物化学、微生物学、人工智能和
风险评估,并具有丰富的经验,在研究
硝基芳烃。 将使用两种计算机技术。 第一、
计算机自动结构评估(CASE),一种人工
该情报计划是为了预测
硝基芳烃的致突变性,将用于鉴定结构
致突变性、遗传毒性和致癌性的决定因素。
二、致癌性预测和电池选择
(CPBS)方法将用于识别合适的电池,
筛选硝基芳烃及其混合物的短期试验
并预测潜在致癌性,包括致癌性
力量 实验研究将针对评估
混合物中化合物的活性。 人工混合物
对硝基芳烃或相关化合物,以及
燃烧排放物与单独的化学品结合,将是
检测致突变性、代谢活化和失活
致突变性、哺乳动物遗传毒性和代谢毒性
生物转化 将讨论三个问题:
活动是加性的或受竞争的影响,
酶促活化,是否鉴定了灭活结构
代表替代生物转化或竞争
以及复杂混合物的存在如何影响
个体的代谢、致突变性和遗传毒性
化学品 解决这些关于外推的问题
从单个成分到混合物,
关于生物利用度,代谢,
遗传毒性、解毒和排泄,用于减少
在评估人类接触危险方面的不确定性
不完全燃烧产物和其他复杂混合物。
英文摘要
The biological activity of nitrated polycyclic aromatic
hydrocarbons (nitroarenes) has ben the subject of extensive study
primarily because of the potent mutagenicity and carcinogenicity
of some nitroarenes as well as their widespread occurrence in the
environment, principally as the result of incomplete combustion
processes. However, most of us are not exposed primarily to
individual compounds but rather to complex mixtures both
outdoors (emissions from automobiles, power plants, etc.) and
indoors (cigarette smoke, heaters, stoves, ovens etc). The
objective of the work proposed in this application is to relate the
genotoxic and carcinogenic activities of individual nitroarenes to
activities of artificial mixtures and extracts of emission
particulates in order to use data for single chemicals to evaluate
the risk of exposure to complex mixtures. The proposed project,
which employs both computerized and experimental
methodologies, will involve professionals with expertise in
chemistry, biochemistry, microbiology, artificial intelligence and
risk assessment, and with extensive experience in the study of
nitroarenes. Two computerized techniques will be used. First,
Computer Automated Structure Evaluation (CASE), an artificial
intelligence program which was developed to predict the
mutagenicity of nitroarenes, will be used to identify structural
determinants of mutagenicity, genotoxicity and carcinogenicity.
Second, the Carcinogenicity Prediction and Battery Selection
(CPBS) method will used to identify appropriate batteries of
short-term tests for screening individual nitroarenes and mixtures
and to predict potential carcinogenicity, including carcinogenic
potency. Experimental studies will be directed towards assessing
the activities of compounds in mixtures. Artificial mixtures of
pairs of nitroarenes or related compounds, as well as extracts of
combustion emissions combined with individual chemicals, will be
tested for mutagenicity, metabolic activation and deactivation of
mutagenicity, mammalian genotoxicity and metabolic
biotransformation. Three issues will be addressed: whether
activities are additive or are influenced by competition for
enzymatic activation, whether inactivating structures identified
by CASE represent alternative biotransformation or competition
and how the presence of a complex mixture influences the
metabolism, mutagenicity and genotoxicity of individual
chemicals. Resolving these questions about the extrapolation
from individual components to mixtures would allow data for
individual chemicals concerning bioavailability, metabolism,
genotoxicity, detoxification and excretion to be used to reduce
uncertainty in the assessment of human risk from exposure in
incomplete combustion products and other complex mixtures.
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会议论文
TRAINING IN COMPUTATIONAL TOXICOLOGY
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批准号:6604002
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项目类别:
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资助金额:$9.02万
-
财政年份:2000
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负责人:HERBERT S ROSENKRANZ
-
依托单位:
TRAINING IN COMPUTATIONAL TOXICOLOGY
-
批准号:6498263
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项目类别:
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资助金额:$8.42万
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财政年份:2000
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依托单位:
TRAINING IN COMPUTATIONAL TOXICOLOGY
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批准号:6080877
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项目类别:
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资助金额:$3.48万
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财政年份:2000
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负责人:HERBERT S ROSENKRANZ
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依托单位:
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批准号:6350804
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项目类别:
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资助金额:$7.25万
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财政年份:2000
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QUANTIFYING NITROARENE GENOTOXICITY IN COMPLEX MIXTURES
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批准号:3252787
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项目类别:
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资助金额:$9.4万
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财政年份:1990
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负责人:HERBERT S ROSENKRANZ
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依托单位:
QUANTIFYING NITROARENE GENOTOXICITY IN COMPLEX MIXTURES
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批准号:3252785
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项目类别:
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资助金额:$9.69万
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财政年份:1988
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负责人:HERBERT S ROSENKRANZ
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依托单位:
ENVIRONMENTAL BIOLOGY
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批准号:3536086
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项目类别:
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资助金额:$10.29万
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财政年份:1978
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负责人:HERBERT S ROSENKRANZ
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依托单位:
ENVIRONMENTAL CARCINOGENESIS
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批准号:3820992
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项目类别:
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资助金额:$0.0万
-
财政年份:--
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负责人:HERBERT S ROSENKRANZ
-
依托单位:
ENVIRONMENTAL CARCINOGENESIS
-
批准号:3939067
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:HERBERT S ROSENKRANZ
-
依托单位:
ENVIRONMENTAL CARCINOGENESIS
-
批准号:3812824
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:HERBERT S ROSENKRANZ
-
依托单位:
ENVIRONMENTAL CARCINOGENESIS
-
批准号:3817018
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:HERBERT S ROSENKRANZ
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依托单位:
海外基金