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  • br Based on previous studies about the


    Based on previous studies about the epigenetic effects of BPA (Mlynarcikova et al., 2013; Bhan et al., 2014; S¸ enyildiz and Ozden, 2015), in present study, we selected 10 nM, 100 nM and 1 mM exposure concentrations of BPS for 24 h for the analysis of changes in DNA methylation. In total, 8 tansposons from randomly selected genes were analyzed, including Ac-like, HERVE, LINE 2, MaLR, Mariner 2, MER 2, MER 4 and SINE-R (Table 1). As shown in Fig. 1, by comparing the sample digested and undigested (take lane 1 and lane 5 as an example), we found that after digestion, the amount of amplified transposons were decreased, indicating that they were methylated. When the same amount of DNA from the control and BPS exposure group were subjected for McrBC digestion (lane 1 to 4), compared with the 5th lane, the weaker or stronger lane of the BPS exposure group (lane 6 to lane 8) means that BPS exposure
    Fig. 1. Methylation level changes in transposons of MCF-7 Oxidopamine under exposure of BPS.
    changes methylation levels of the transposons. Our results showed that for MaLR and Mariner 2, the amplified transposons in the exposure group with 10 nM and 100 nM BPS were the same as control group, while that in the 1 mM BPS group were decreased, indicated that 1 mM of BPS exposure induced the hypermethylation of these transposons. While for MER2, 100 nM BPS can also induce its hypermethylaton (Fig. 1). The results suggested that BPS expo-sure could increase the methylation level of transposons.
    It was reported that BPA could cause epigenetic changes, which was one of the possible mechanism through which BPA induces human diseases (Rezg et al., 2014). However, there was no formal assessment on whether BPS could induce epigenetic effects on human. Our results here showed that BPS exposure influenced the methylation status of transposons. Transposons are firmly regu-lated from early embryonic development and during the entire course of human life. A growing number of studies have delineated that epigenetic mechanisms may also control transposon reac-tivation with subsequent effects on carcinogenesis (Chenais, 2015). DNA methylation in transposons is a key mechanism defending against their transposition activities (de la Rica et al., 2016; Hu et al., 2017; Zheng et al., 2017). As DNA methylation status affects the mobility of transposons and then influences the genomic instability as well as induces oncogenic activation and transcriptional dysre-gulation, in this work we analyzed changes of DNA methylation in transposons induced by BPS to evaluate the effects of BPS on breast cancer cells. We found that BPS exposure increased DNA methyl-ation levels of several of the analyzed transposons. This result not only indicated that BPS could induce genomic DNA methylation changes, but also implicated that BPS may contribute to dysregu-lation of gene expression.
    Mechanism by which BPS induced DNA methylation may similar to other environmental chemicals. The mechanism of environ-mental chemicals induced changes in global DNA methylation status may rely on two often described hypotheses. First, evidence has demonstrated the direct action of environmental chemicals on the function of DNMT and TET enzyme families. Second, evidence has also shown that environmental chemicals may change the availability of SAM. Besides, changes in gene-specific DNA methylation patterns may because of that environmental chemicals exposure trigger transcription factors, and the presence or absence of transcription factors on the DNA denies or allows access to the DNA methylation, then influence the observed site-specific pat-terns of methylation (Martin and Fry, 2018).
    3.2. BPS exposure changed methylation level of breast cancer-related genes
    The Human Breast Cancer EpiTect Methyl II Signature PCR Array was used to analyze the changes in methylation status of 22 tumor 
    suppressor gene promoters whose hypermethylation was reported to occur frequently in a variety of breast tumors. The results showed that the methylation status of BRCA1, CCNA1, CCND2, CDH1, CDH13, CDKN1C, MGMT, PRDM2, PTEN, PTGS2, PYCARD, SFN, THBS1, TNFRSF10C, ESR1 in the exposure group of 1 mM BPS differed significantly (p < 0.05) from the methylation status of control group. Most of these genes showed higher methylation, except CCND2, CDH13 (Table 2). However, according to the instructions of the manufacturer, a threshold of 20% changes in methylation level was considered to be hypermethylated or hypomethylated. Only methylation level changes of CDH1, SFN, TNFRSF10C exceeded the threshold for hypermethylation (Table 2).