Arecoline-induced changes of poly-ADP-ribosylation of cellular proteins and its influence on chromatin organization

Arecoline, the major alkaloid of betel nut (Areca catechu L.) and a suspect ed carcinogen, has been implicated in human cancers of various sites. A con siderable portion of the world's population is constantly exposed to arecol ine due to the habit of masticating betel nuts. The present work relates to the study of early molecular events following chronic arecoline exposure a t a dose of 10 mu g/ml to Swiss albino mice. Poly-ADP-ribosylation of all c ellular proteins, histones and poly-ADP-ribose polymerase were studied in b one marrow and spleen cells and correlated with the organizational status o f the chromatin. While most proteins showed lowering of their poly-ADP-ribo sylation following arecoline treatment, only histone protein H1 in spleen c ells and H2B in bone marrow cells exhibited an increase. The chromatin of b oth the tissues was progressively relaxed upon arecoline exposure. The impl ications of these changes have been discussed regarding the process of init iation of arecoline-induced carcinogenesis. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.