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Rat liver histone modifications and their relationship to DNA-dependent RNA polymerase activities during α-hexachlorocyclohexane induced liver proliferation

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Summary

The time course of histone acetylation, methylation and phosphorylation during α-hexachlorocyclohexane (α-HCH) induced liver cell proliferation has been studied and correlated to other biochemical events in rat liver caused by α-HCH. Both in vitro acetylation and methylation showed an initial increase 1 and 2 h after α-HCH which obviously precedes the beginning of increased nuclear in vitro RNA synthesis. Separation of in vitro acetylated liver histones isolated 1 and 2 h after α-HCH application results in a preferential accumulation of radiactive acetate in the range of F 3, F 2b, F 2a2 histone fractions and in F 2a1. A second peak of increased histone acetylation at 24 h and methylation at 36 h occurs during a period of increased nuclear RNA polymerase activities and the beginning increase of DNA synthesis. An increased in vitro histone phosphorylation was measured 42 h after α-HCH application. From the different time courses of these nuclear events it seems possible that the early histone acetylation and methylation might be involved in the beginning increase of transcriptional activity. Further experiments will be necessary to find out whether the α-HCH induced histone modifications occurring 1, 2 h and 24, 36, 42 h are biologically significant in the sense of a causal connection for α-HCH caused increase of transcriptional activity, DNA replication or enzyme induction or whether they are independent of each other and merely coincide.

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  1. Pharmakologisches Institut der Freien Universität Berlin, Thielalee 69/73, D-1000, Berlin 33

    H. -I. Sarkander, M. Kemmerle & W. Brade

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  1. H. -I. Sarkander
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  2. M. Kemmerle
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  3. W. Brade
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Parts of the results have been reported at the 15. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft in Mainz 1974.

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Sarkander, H.I., Kemmerle, M. & Brade, W. Rat liver histone modifications and their relationship to DNA-dependent RNA polymerase activities during α-hexachlorocyclohexane induced liver proliferation. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 39–53 (1974). https://doi.org/10.1007/BF00499971

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