CHROMATIN PROTEINS AS A POSSIBLE TARGET FOR ANTI-TUMOR AGENTS - ALTERATIONS OF CHROMATIN PROTEINS IN DIBROMODULCITOL TREATED YOSHIDA TUMORS

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). © 1979.