Perfluorooctane sulfonate affects

Perfluorinated compounds have raised concern due to their potential 16 association with detrimental postnatal outcomes in animals and humans. We tested the effects 17 of perfluorooctane sulfonate (PFOS) on a human pluripotent teratocarcinoma (known as 18 NCCIT) cells as an in vitro prototype for developmental toxicity in mammals. NCCIT 19 contains stem-cells able to differentiate into endoderm, mesoderm and ectoderm. We tested 20 our cell model using a teratogenic compound, retinoic acid (RA), a cytotoxin, nocodazole 21 (ND), and PFOS. We assayed cells proliferation, morphology and expression of stem cell and 22 germ layer marker genes. PFOS reduced NCCIT cell proliferation in a concentration23 dependent manner and induced morphological changes in cell cultures that resembled 24 ectodermal phenotypes. A tendency towards a differentiated state in NCCIT was confirmed 25 by real-time gene expression. PFOS triggered up-regulation of the gene nestin, indicative of 26 ectodermal lineage differentiation, and interfered with the expression of the pluripotency 27 stem-cell marker TERT. PFOS produced effects on both cells proliferation and differentiation, 28 although not as severe as those observed for RA and ND, at levels that fall within the range of 29 concentrations found in animal and human plasma. We discuss our findings in the context of 30 possible interference of PFOS with the processes governing the early development of 31 mammalian tissues. 32 33