Jalal Nasir, Surendranath Austin R, Pathak Janak L, Yu Shi, Chung Chang Y
Department of Cellular and Molecular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Tianjin, 300072, Nankai district, People's Republic of China.
Coorg Institute of Dental Sciences, Virajpet, Coorg, 571218, India.
Toxicol Rep. 2017 Dec 16;5:76-84. doi: 10.1016/j.toxrep.2017.12.013. eCollection 2018.
Bisphenol A (BPA) is one of the most widely used synthetic compounds on the planet. Upon entering the diet, its highest concentration (1-104 ng/g of tissue) has been recorded in the placenta and fetus. This accumulation of BPA can have many health hazards ranging from the easy to repair single strand DNA breaks (SSBs) to error prone double strand DNA breaks (DSBs). Although the Human liver can efficiently metabolize BPA via glucuronidation and sulfation pathways, however the by-product Bisphenolquinone has been shown to act as a DNA adduct. Low doses of BPA have also been shown to interact with various signaling pathways to disrupt normal downstream signaling. Analysis has been made on how BPA could interact with several signaling pathways such as NFκB, JNK, MAPK, ER and AR that eventually lead to disease morphology and even tumorigenesis. The role of low dose BPA is also discussed in dysregulating Ca homeostasis of the cell by inhibiting calcium channels such as SPCA1/2 to suggest a new direction for future research in the realms of BPA induced disease morphology and mutagenicity.
双酚A(BPA)是全球使用最广泛的合成化合物之一。进入饮食后,在胎盘和胎儿中记录到其最高浓度(1 - 104纳克/克组织)。BPA的这种积累会带来许多健康危害,从易于修复的单链DNA断裂(SSB)到容易出错的双链DNA断裂(DSB)。尽管人类肝脏可以通过葡萄糖醛酸化和硫酸化途径有效代谢BPA,然而其副产物双酚醌已被证明可作为DNA加合物。低剂量的BPA也已被证明可与多种信号通路相互作用,从而扰乱正常的下游信号传导。已经分析了BPA如何与几种信号通路相互作用,如NFκB、JNK、MAPK、ER和AR,这些最终会导致疾病形态甚至肿瘤发生。还讨论了低剂量BPA通过抑制钙通道(如SPCA1/2)来失调细胞钙稳态的作用,为未来BPA诱导的疾病形态和致突变性领域的研究指明了新方向。