The effects of pilocarpine nitrate upon the mitotic index of mouse bone marrow cells

Aneuploidies are the most common chromosomal causes for spontaneous abortions and constitute a major part of genetic disorders among the neonates. Aneuploidy producing agents (aneugens) pose serious genetic hazards to the human population. Therefore, testing for aneuploidy induction should be part of the requirement in drug safety guidelines. The aneugenic potential of pilocarpine nitrate, an alkaloid drug used as an ophthalmic solution was screened by chromosome analysis studies in the bone marrow cells of mice. Using the technique developed by Miller and Adler (1989) we evaluated changes in the mitotic index (MI), induction of chromatid contraction and spreading (C-mitoses) and decrease of anaphase frequencies as indicators of the aneuploidy inducing potency of the drug. Concentrations of pilocarpine nitrate of 4, 8 and 12 mg/kg body weight were administered intraperitoneally to mice. Colchicine-treated and water-treated animals formed the positive and negative controls. The data obtained in the cytogenetic analysis of both dose-response and time-response studies showed a significant induction of C-mitotic effects in the mouse bone marrow. The positive results indicated that the drug is a potential aneugen and should be further evaluated.