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Wiebel, F.J. ; Klose, U. ; Kiefer, F.

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro: H4IIEC3-derived 5L hepatoma cells as a model system.

Toxicol. Lett. 55, 161-169 (1991)

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was investigated for its toxicity in 5L-cells, descendants 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 analysís, 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.

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