Chromatin proteins as a possible target for antitumour agents: Alterations of chromatin proteins in dibromodulcitol treated Yoshida tumors

A. Jeney, É Dzurillay, K. Lapis, É Valkó

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Abstract

The effect of dibromodulcitol (DBD) on Yoshida sarcoma chromatin components has been investigated. Measurements on the radioactivity of nuclear components after in vivo treatment with [3H] DBD for 1 h indicated preferential drug binding to the high molecular weight component of the nuclear residual acidic protein (non-histones) and also to Histone 1 (H1) (very lysine rich, F1). Two-hour DBD treatment resulted in partial degradation and reduced [3H] leucine incorporation into the same fractions of chromatin. However, 6 h after DBD treatment, the synthesis of the degraded chromatin proteins began and by 24 h was completed. During the same treatment period the composition of chromatin showed a remarkable alteration; 2 h after DBD treatment the amount of the nuclear residual acidic proteins relative to DNA decreased by approx. 50%, but returned to control value 24 h after drug treatment. This in conjunction with the data on [3H] leucine incorporation suggests that certain chromatin proteins are degraded and subsequently newly synthesised after DBD treatment resulting in an exchange of chromatin components. The formation of a nucleohistone complex between H1 and DNA was inhibited by pretreatment of H1 with DBD, dianhydrodulcitol (DAD) and bischloroethylnitrosourea (BCNU).

Original languageEnglish
Pages (from-to)349-361
Number of pages13
JournalChemico-Biological Interactions
Volume26
Issue number3
DOIs
Publication statusPublished - Aug 1979

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ASJC Scopus subject areas

  • Toxicology

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