COMPUTATIONAL MODELING OF ESTROGEN METABOLISM

摘要

Oxidative estrogen metabolites have been implicated inrnthe development of breast cancer. An assessment ofrnbreast cancer risk due to varying patterns of lifetimernestrogen exposure and genetic variations depends on thernability to estimate the concentration dynamics ofrnoxidative metabolites. This requires modeling the systemrnof metabolic reactions implicated in the formation ofrnDNA adducts that are linked to mutagenesis and cancer.rnThe proposed computational model of metabolism reliesrnon a first order approximation of reaction kineticsrncombined with an experimentally driven estimation of itsrnparameters. The performance of the model is satisfactoryrnin the sense that it replicates the experimentally knownrnprofiles of metabolite concentrations. However, thernprediction capacity of the model would greatly benefitrnfrom the inclusion of new experimental data as theyrnbecome available.