Arsenic can mediate skin neoplasia by chronic stimulation of keratinocyte-derived growth factors

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

“…NHEK and HaCaT and HEL30 keratinocytes are epidermal cells used to characterize the effects of arsenic on proliferative gene expression (5,35), cytokine and growth factor expression (6,8,36), and the role reactive oxygen species (ROS) play in epidermal dysfunction and signal transduction modulation (37)(38)(39). Although well suited with respect to target tissue, these cells present unique phenotypes that may display different responses to oxidative stress-inducing agents like arsenic.…”

“…Skin cancer is a common manifestation of arsenic exposure, and keratinocytes are a primary target of arsenic in vivo (3)(4)(5)(6)(7)(8)(9). Both primary and immortalized keratinocytes have been used in studies examining arsenic-induced skin cancer and epidermal toxicity.…”

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

“…As described below, members of the GATA family of transcription factors that are typically associated with the hematopoietic system have been found to coexpress with the transgene (Trempus et al, 1998b;Delker et al, 1999;Humble et al, submitted). It has also been reported that a reduction in GM-CSF reduces tumor multiplicity in Tg.AC mice (Germolec et al, 1997). The expression of CD34, a 105-120 kDa glycoprotein expressed in hematopoietic stem and progenitor cells, was examined in the skin and intense membrane staining was found in cells in Figure 3 Expression of ras transgene message and PCNA.…”

Characterization of gene expression changes associated with MNNG, arsenic, or metal mixture treatment in human keratinocytes: application of cDNA microarray technology.

“…Cells (1 × 10 4 /cm 2 ) were plated in 25-cm 2 culture flasks in triplicate. Viable cells at 5,8,10,12,15, and 17 days after initial plating were counted by trypan blue exclusion on a hemocytometer. Culture medium was changed every 3 days.…”

“…Chronic exposure to As leads to skin disorders such as hyperkeratosis and, in many cases, carcinogenesis (12,13). Both As and Cr, a well-known skin sensitizer, have substantial effects on epidermal keratinocytes in vitro and in vivo; these metals have been shown to alter expression of numerous growth regulatory factors, to stimulate cell proliferation at low concentrations, and to inhibit the normal process of differentiation (11,(14)(15)(16)(17)(18)(19). They have not, however, been shown to be directly transforming in this cell type.…”