Abstract 3186: Transplacental arsenic exposure modifies the number of hair follicle keratinocytes stem cells and alters their cell-cycle control

Abstract

Abstract Drinking water contamination with arsenic is a worldwide problem and a concern in some areas of the United States, especially in the West (California, Nevada, Alaska and Utah) and small areas of New England. Inorganic arsenic is considered a human carcinogen with many target tissues such as the skin, urinary bladder and lung; and characterizing its mechanisms of action is key to designing methods of intervention. Arsenic has transplacental carcinogenic activity, and since their fetal abundance, stem cells (SCs) seem to be a main target of arsenic exposure during gestation. We have established that fetal arsenic exposure via the maternal drinking water, leads to a decrease number of keratinocyte's stem cells (KSC) in mouse epidermis of the offspring. Biochemical analysis of these KSCs shows increased mRNA levels of the cell-cycle regulators cyclin D1 and CDK4. Supporting this observation, overexpression of CDK4 in KSCs mimics arsenic exposure as demonstrated by the reduced number of KSCs, and the decreased number of benign skin tumors, and severe rise in the rate of malignant conversion to squamus cell carcinomas. We expect that these studies will enable to determine the consequence of in utero arsenic exposure on the proliferative potential of KSCs and the impact on the selection of KSCs that give origin to skin tumors with high risk of malignant conversion. Therefore, these studies will contribute to understanding how early alterations of somatic stem cells results in functional changes that impact a late stage of tumorigenesis such as malignant progression. Citation Format: Paula L. Miliani de Marval, Sun Hye Kim, Marcelo L. Rodriguez-Puebla. Transplacental arsenic exposure modifies the number of hair follicle keratinocytes stem cells and alters their cell-cycle control. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3186. doi:10.1158/1538-7445.AM2014-3186