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 suspected carcinogen, has been implicated in human cancers of various sites. A considerable portion of the worldʹs population is constantly exposed to arecoline due to the habit of masticating betel nuts. The present work relates to the study of early molecular events following chronic arecoline exposure at a dose of 10 μg/ml to Swiss albino mice. Poly-ADP-ribosylation of all cellular proteins, histones and poly-ADP-ribose polymerase were studied in bone marrow and spleen cells and correlated with the organizational status of the chromatin. While most proteins showed lowering of their poly-ADP-ribosylation following arecoline treatment, only histone protein H1 in spleen cells and H2B in bone marrow cells exhibited an increase. The chromatin of both the tissues was progressively relaxed upon arecoline exposure. The implications of these changes have been discussed regarding the process of initiation of arecoline-induced carcinogenesis.