A single neonatal administration of Bisphenol A induces higher tumour weight associated to changes in tumour microenvironment in the adulthood

作者：Isabel Palacios Arreola Margarita; Elizabeth Nava Castro Karen; Hugo Del Rio Araiza Victor; Yazmin Perez Sanchez Nashla; Morales Montor Jorge^*

来源：Scientific Reports, 2017, 7(1): 10573.

DOI：10.1038/s41598-017-10135-1

BPA is an oestrogenic endocrine disrupting chemical compound. Exposure to BPA in as early as pregnancy leads to lifelong effects. Since endocrine and immune systems interact in a bidirectional manner, endocrine disruption may cause permanent alterations of the immune system, affecting a future anti-tumoral response. Neonate (PND 3) female syngeneic BALB/c mice were exposed to a single dose of 250 mu g/kg BPA. Once sexual maturity was reached, a mammary tumour was induced injecting 4T1 cells in situ, these cells are derived from a spontaneous adenocarcinoma in a BALB/c mouse and therefore allows for an immunocompetent recipient. After 25 days of injection, showing no major endocrine alterations, BPA-exposed mice developed larger tumours. Tumour leukocytic infiltrate analysis revealed a higher proportion of regulatory T lymphocytes in the BPA-exposed group. RT-PCR analysis of tumour samples showed a decreased expression of TNF-alpha and IFN-gamma, as well as the M2 macrophage marker Fizz-1 in the BPA-exposed group. Flow cytometry analysis revealed differences in ER alpha expression by T lymphocytes, macrophages and NK cells, both associated to BPA exposure and tumour development. These findings show a new aspect whereby early life BPA exposure can contribute to breast cancer development and progression by modulating the anti-tumoral immune response.

• 出版日期2017-9-5