Systems and methods for using mechanistic network models in systems toxicology
A causal network model, technology of biological systems, applied in the field of systems and methods using mechanistic network models in system toxicology, can solve problems such as hazards
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[0131] Example 1: Xenobiotic Metabolism Networks as Biomarkers for CS Exposure on In Vivo and In Vitro Systems
[0132]Humans and other mammals are equipped with elaborate mechanisms to address carcinogens and other toxic compounds; the defense system includes oxidation reactions by cytochrome P450 enzymes (CYP; phase 1), followed by conjugation reactions by phase 2 enzymes. These enzymes in turn convert lipophilic chemical compounds into hydrophilic water-soluble forms that can be eliminated from the body [Burchell, B. et al. (2005) Substrate Specificity of Human Hepatic Udp-Glucuronosyl transferases. Methods in enzymology. 400, 46-57; Guengerich, F.P. ( 2001) Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol. 14, 611-50; Transformation of polycyclic aromatic hydrocarbons (PAHs), also present in cigarette smoke (CS), can lead to the generation of oncogenic intermediates capable of interacting with genomic DNA [Kim, J.H...
example 2
[0137] Example 2: Mechanistic approach for the quantification of perturbed processes in the lungs of C57 / B16 mice following CS exposure and cessation
[0138] Chronic obstructive pulmonary disease (COPD) is the leading cause of chronic disease and death in the world [Mathers, CD. and Loncar, D. (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS medicine. 3, e442]. C57 / B16 mice exposed to CS provide valuable insight into emphysema initiation and development [Churg, A. Cosio, M. and Wright, J.L. (2008) Mechanisms of cigarette smoke-induced COPD: insights from animal models. American Journal of Physiology-Lung Cellular and Molecular Physiology. 294, L612 -L631], although this mimics only certain aspects of early human COPD characterized by reduced lung function, abnormal inflammatory responses in the airways, small airway remodeling and destruction of alveolar tissue [Pauwels, R.A. and Rabe, K.F. (2004 ) Burden and clinical features of chronic ob...
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