【摘要】 以典型天然雌激素雌二醇为代表,以人体乳腺癌细胞MCF-7增殖为手段,检验了六氯苯与雌二醇共同作用时的内分泌干扰活性及其机理.结果发现六氯苯具有强烈的内分泌干扰活性,但与雌二醇混合后,呈现明显的拮抗效应,内分泌干扰活性被显著抑制.机理分析表明六氯苯、雌二醇、二者混合物都可以干扰雌激素受体和胞外信号调节激酶(ERK)信号通路、激活转录因子、诱导细胞增殖.路径分析表明,六氯苯与雌二醇的拮抗作用与雌激素受体通路无关,主要原因是雌二醇降低了六氯苯对ERK的活化程度、降低了p-ERK蛋白的表达、从而干扰了丝裂原活化蛋白激酶信号转导.转录因子分析表明,雌二醇弱化六氯苯内分泌干扰活性的主要原因是降低了c-Myc蛋白表达.上述发现为六氯苯的控制提供了理论依据.更多还原

【Abstract】 Hexachlorobenzene’s(HCB’s)estrogenicity change and potential mechanisms when mixing with a typical natural estrogen,17-Estradiol(E2),were investigated.Human breast cancer cell MCF-7increase examination was used.The results showed that HCB had very strong estrogenicity,but the mixture of HCB and E2showed strong rivalry effect,i.e.,E2and HCB greatly weakened each other on endocrine disrupting effect.Mechanism analyses showed that E2and HCB could interfere with the endocrine system via the endocrine receptor channel and the MAPK signal channel.The rivalry effect between E2and HCB was unrelated with the traditional endocrine receptor channel,but depended strongly on the non-traditional ERK channel.E2decreased the HCB activation of ERK protein,and decreased the expression of p-ERK protein,thus interrupting the transcription of MAPK signal.The transcription factor analyses showed that E2weakened the function of HCB mainly by decreasing the expression of c-Myc protein.更多还原