摘要
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,doseresponse 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] ) .
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,doseresponse 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] ） .
出处
《中国比较医学杂志》
CAS
2013年第1期69-80,共12页
Chinese Journal of Comparative Medicine
关键词
基础医学
呼吸生理
呼吸运动
人体生理学
Xenobiotic drugs
Xenobiotic chemicals
In vitro assays
High throughput screening
Cancer
TP53
FOS
JUN
Steroidal and non-steroidal nuclear receptors
MAP kinases
