Bisphenol A(BPA)and its alternatives are used mainly in the manufacture of chemical products,such as the synthesis of polycarbonates,epoxy resins and thermal paper.BPA has a plenty of transformation pathways in animals,bacteria and plants.Therefore,human are exposed to BPA almost everywhere.The available result suggests that BPA exposure is closely related to breast cancer.However,toxicological effects of BPA alternatives have not been definite during the process from inflammatory hyperplasia to carcinoma and metastasis in human breast cancer model.DNA methylation plays essential role in many biological processes such as nuclear reprogramming,embryogenesis,gene transcription and genome stability.Recently,aberrant DNA methylation has been found to be associated with the various human diseases.Genomic DNA hypomethylation has been discovered in many human cancers,such as breast cancer and colorectal cancer,and it will be an important biomarker for clinical evaluation of human cancer.In our study,the human breast cancer xenograft-bearing nude mice model will be employed to study the changes of DNA methylation after BPA alternatives exposure during the different periods of breast cancer formation.A high performance liquid chromatography-mass spectrometry method was developed for the detection of genomic DNA methylation levels.By calculating the ratio of 5mdC to dG,average DNA methylation level of mice tissues ranged from 3.12%to 5.73%.Comparing the data from control group with that of the BPS-exposure group,average DNA methylation level of BPS-exposure group(3.23±0.11%)was relatively lower than that of control group(4.12±0.32%).The lower global DNA methylation level of BPS-exposure group may be associated with the aberrant methylation reprogramming.The results of our study will provide strong support for screening of secure alternative of BPA.