Effects of acute and chronic arsenic exposure of human-derived keratinocytes in an In Vitro human skin equivalent system: a novel model of human arsenicism

Toxicology in Vitro : an International Journal Published in Association with BIBRA
Walter T KlimeckiG T Bowden

Abstract

An organotypic culture (OTC) of a human keratinocyte cell line (HaCaT) over a human fibroblast-embedded collagen gel was used to model human epidermis in arsenicism, a syndrome that currently lacks valid experimental models. Keratinocytes were exposed acutely or chronically to a mixture of arsenate (0.5 muM), monomethylarsonic acid (MMA; 0.5 muM) and dimethylarsinic acid (DMA; 1.5 muM), or to the individual components of the mixture. OTCs were assayed for microscopic morphology, the proliferating cell marker, Ki-67, labelling and cytokeratin expression. Acute exposures resulted in an epidermal phenotype that accurately modelled early human lesions, including hyperkeratosis, acanthosis and keratin 16 induction. Chronic exposures resulted in a de-differentiated epidermal phenotype with focal nests of keratinocytes growing into the collagen gel. The keratin 8 18 pair was induced by either acute or chronic arsenic exposure, as was the proliferating cell marker, Ki-67. Exposure of keratinocytes to individual arsenic compounds demonstrated that all arsenic mixture-induced changes could be duplicated by exposure to arsenate alone. In contrast, MMA and DMA were inactive. This study establishes OTC as a useful model of arsenicism, and i...Continue Reading

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Dec 10, 1998·The American Journal of Pathology·D R GermolecM I Luster
Sep 18, 2013·Critical Reviews in Toxicology·Samuel M CohenMichal Eldan
Feb 20, 2007·Toxicology and Applied Pharmacology·Mercedes MezaWalter T Klimecki
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