EFFECTS OF CHRONIC LOW-DOSE ARECOLINE ADMINISTRATION ON THE MACROMOLECULAR COMPONENTS OF BONE-MARROW AND SPLEEN-CELLS OF MICE

Background - An association between arecoline, the major, natural alka loid of betel nut, and carcinogenesis has been established. However, l ittle is known about the early molecular events following low-dose chr onic exposure to arecoline in an in-vivo system, Methods - Swiss albin o mice were exposed to 10 mg/ml of arecoline in their drinking water f or up to five weeks, The effects on cell number, DNA, RNA, total prote in and histone content of bone marrow and spleen were monitored. Poly- ADP-ribosylation of total cellular proteins was also measured. Results - Cell number, DNA and total protein content were not significantly c hanged upon arecoline exposure. An immediate increase in the histone c ontent of bone marrow cells was observed, in contrast to spleen cells. On the other hand, the former showed an unchanged level of poly-ADP-r ibosylation while it was reduced in the latter, Conclusions - The resu lts suggest that arecoline exposure creates molecular events which pri me the genome for carcinogenesis in bone marrow and spleen cells, desp ite the physiological differences between them.