Induction of terminal differentiation in cultured human keratinocytes by polychlorinated aromatic hydrocarbons as measured by cell size analysis.
Polychlorinated aromatic hydrocarbons modulate the proliferation and differentiation of human epidermal cells in vivo and in culture. One of the earliest events in the process of terminal differentiation is the increase in cell size. In this report the usefulness of morphometric cell size analysis as a quantifiable marker for chemical-induced differentiation was examined. Concentration-related increases in cell size distribution were induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 2,3,4,7,8-pentachlorodibenzofuran in normal human keratinocytes and cells from an SV40-transformed keratinocyte cell line (SVK14) whereas the analog 1,2,3,4-tetrachlorodibenzo-p-dioxin did not affect the cell size distribution up to a concentration of 100 nM. The minimal effective concentrations of five 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins/dibenzofurans and a coplanar polychlorbiphenyl necessary to induce an increase in cell size distribution were determined in SVK14 cells. It was found that the potency of these compounds relative to that of 2,3,7,8-TCDD correlated well with the toxicity equivalency factors observed in other test systems. This indicates that the keratinocyte cell assay is a useful method for establishing the relative potency of various "dioxins" and their mixtures.
Van Pelt
F N
FN
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Hassing
I G
IG
Stelling
M A
MA
Seinen
W
W
Blaauboer
B J
BJ
D002478:Cells, Cultured; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D015603:Keratinocytes / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity
D006843:Hydrocarbons, Chlorinated; D000072317:Polychlorinated Dibenzodioxins; D011078:Polychlorinated Biphenyls