Chromosome aberrations in mouse bone marrow cells following treatment in vivo with vinblastine and colcemid

Abstract

The present study was undertaken to determine if chemicals that are capable of inducing mitotic arrest and aneuploidy can also induce chromosomal breakage. Two chemicals, vinblastine and Colcemid, were selected to be studied. Their potentially clastogenic effects were investigated in mouse bone marrow cells in vivo. Two doses of vinblastine, 10⁻⁵ M (9 mg/kg) and 10⁻⁶ M (0.9 mg/kg), and one dose of Colcemid 10⁻⁴ M (37 mg/kg), were administered to mice as single intraperitoneal injections. Bone marrow preparations were made at multiple time periods after injections, ie, 17, 24, 48, 72, and 96 hr. Both these agents, at the concentrations tested, induced mitotic arrest of bone marrow cells within 5 hr after injection. In recovering bone marrow cell populations, 2–3 days after drug administration, significantly elevated levels of chromosomal breakage (mainly the chromatid type) were observed. Vinblastine was found to be much more potent than Colcemid. Since both of these agents affect mainly microtubules, their actions to cause chromosomal breakage are likely to be indirect. Several possible clastogenic mechanisms such as interference with DNA synthesis, active metabolites, and cytoplasmic endonucleases are discussed.