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Xenobiotic effects in cancer related pathways-high throughput screening and proof of concept in animal models

Ursula E. Schumacher

中国比较医学杂志2013,Vol.23Issue(1):69-80,12.
中国比较医学杂志2013,Vol.23Issue(1):69-80,12.DOI:10.3969.j.issn.1671.7856.2013.001.015

Xenobiotic effects in cancer related pathways-high throughput screening and proof of concept in animal models

Xenobiotic effects in cancer related pathways-high throughput screening and proof of concept in animal models

Ursula E. Schumacher1

作者信息

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摘要

Abstract

Xenobiotic drugs and chemicals directly interact with DNA, proteins, or other biomolecules in cells. These direct interactions with molecular targets may trigger a series of downstream effects on metabolic-biochemical and regulatory-signaling networks that can invoke cellular consequences leading to adaptive homeostatic or adverse pathological responses. Regulators for drug and chemicals safety have therefore since long required the testing of toxicity in animal models before drugs and pesticides can enter the market. The US National Research Council of the National Academy of Sciences, in its report, Toxicity Testing in the 21st Century: a Vision and a Strategy[1], proposed that toxicity testing should become less reliant on apical endpoints from whole animal tests and eventually rely instead on quantitative, dose-response models based on information from in vitro assays and in vivo biomarkers, which can be used to screen large numbers of chemicals.The present paper reports about a combination of HTS in vitro assays that can be used to study the potential tumorigenic effect of xenobiotics (drug targets, environmental chemicals) via a set of "sentinel" genes[2] that are functionally interrelated based on evidence weighted functional linkage network (FLN) log-likelihood scores (Linghu et al[3]).

关键词

Xenobiotic drugs/ Xenobiotic chemicals/ In vitro assays/ High throughput screening/ Cancer/ TP53/ FOS/ JUN/ Steroidal and non-steroidal nuclear receptors/ MAP kinases

Key words

Xenobiotic drugs/ Xenobiotic chemicals/ In vitro assays/ High throughput screening/ Cancer/ TP53/ FOS/ JUN/ Steroidal and non-steroidal nuclear receptors/ MAP kinases

分类

医药卫生

引用本文复制引用

Ursula E. Schumacher..Xenobiotic effects in cancer related pathways-high throughput screening and proof of concept in animal models[J].中国比较医学杂志,2013,23(1):69-80,12.

中国比较医学杂志

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1671-7856

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