Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro: H4IIEC3-derived 5L hepatoma cells as a model system.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was investigated for its toxicity in 5L-cells, descendents of the hepatoma line H4IIEC3. TCDD reduced the proliferation of 5L-cells by about 50%, with half-maximum inhibition at 0.1-0.3 nM concentrations. As shown by flow cytometric analysis, TCDD blocked the entry of 5L-cells into the S-phase, but did not hinder their progression through S and G2/M to the G1 phase. There was a marked increase in cell volume concomitant with the inhibition of growth. Both effects became apparent as early as 4-8 h after TCDD exposure. The parental line H4IIEC3/G- and the variant lines H4IIEC3/T, p4 and H5 were insensitive to the growth-inhibitory effect of TCDD. In view of the rapid onset of effects which can readily be detected and quantitated, 5L-cells offer a highly useful system for analysing the mechanism of action of TCDD at the cellular level.
Wiebel
F J
FJ
GSF-Institute of Toxicology, Gesellschaft für Strahlen- und Umweltforschung, Neuherberg F.R.G.
Klose
U
U
Kiefer
F
F
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*
D000072317:Polychlorinated Dibenzodioxins; D004247:DNA