Proteomic analysis of human breast cell lines using SELDI-TOF MS shows that mixtures of estrogenic compounds exhibit simple similar action (concentration additivity).
Endocrine modulating chemicals in the environment are possible causative agents of a number of human diseases. Many of these compounds act on the same molecular target, and hence risk assessment requires consideration of their possible combined effects. Here, we studied the combined effects of 17beta-estradiol, genistein, bisphenol A and endosulfan on MCF-7 cells. Full concentration-effect curves for cell proliferation were obtained for each compound and used to identify appropriate concentrations for investigating the effects of binary mixtures of the compounds. Protein profiling by surface-enhanced laser desorption/ionization time of flight mass spectrometry was performed to identify responsive proteins. Treatment with each of the compounds produced similar protein profile changes. Prominent and consistent changes were seen in 12 protein ions. Cell proliferation and protein levels responded monotonically to the estrogens, with identifiable no observable effect concentrations in all cases. Binary mixtures of the compounds produced effects on cell proliferation and on each of the responsive protein ions that were fully consistent with concentration additivity. Thus, no reason to deviate from the application of the principles of dose-response and dose additivity in the risk assessment of combinations of estrogenic compounds was found in this study.
Zhu
Zheying
Z
Department of Experimental Medicine and Toxicology, Division of Investigative Science, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK. z.zhu@imperial.ac.uk
Edwards
Robert J
RJ
Boobis
Alan R
AR
D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
D004967:Estrogens; D009363:Neoplasm Proteins