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

Walter Klimecki, A. H. Borchers, R. E. Egbert, Raymond B Nagle, D. E. Carter, G. T. Bowden

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 μM), monomethylarsonic acid (MMA; 0.5 μM) and dimethylarsinic acid (DMA; 1.5 μM), 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 implicates inorganic arsenic as the ultimate carcinogen.

Original languageEnglish (US)
Pages (from-to)89-98
Number of pages10
JournalToxicology in Vitro
Volume11
Issue number1-2
DOIs
StatePublished - Feb 1997

Fingerprint

Arsenic
Keratinocytes
Skin
Dynamic mechanical analysis
Keratin-16
Collagen
Gels
Cacodylic Acid
Keratin-8
Keratin-18
Arsenicals
Phenotype
Fibroblasts
Keratins
Cell culture
Epidermis
Carcinogens
Labeling
Theoretical Models
Cells

ASJC Scopus subject areas

  • Toxicology

Cite this

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. / Klimecki, Walter; Borchers, A. H.; Egbert, R. E.; Nagle, Raymond B; Carter, D. E.; Bowden, G. T.

In: Toxicology in Vitro, Vol. 11, No. 1-2, 02.1997, p. 89-98.

Research output: Contribution to journalArticle

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