Bisphenol A (BPA) the mighty and the mutagenic

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 Bisphenol-o-quinone 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 Ca2+ 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. Keywords: Bisphenol A (BPA), DNA damage, Cancer, Mutations, Ca2+ homeostasis, SPCA1 inhibition, IGF1

Low-dose bisphenol A (BPA)-induced DNA damage and tumorigenic events in MCF-10A cells

The carcinogenic capacity of Bisphenol A (BPA) at nano-molar concentrations of 8.73 and 17.47 nM (in culture) was evaluated on both normal breast epithelial cells (MCF-10A) and breast cancer cells (MCF-7). The highest DNA damage was recorded at 6 h and MCF-10A cells showed significant increase of IGF1R protein while mRNA expression was unchanged; however, the converse was true for MCF-7 cells. Homology modeling predicted the structure of SPCA1/2 and indicated BPA binding within catalytic domain. Our data indicated that BPA caused detectable DNA damage, inhibited cellular SPCA1/2 protein which eventually dysregulated Ca2+-dependent IGF1R