ETOPOSIDE (VP-16) - CYTOGENETIC STUDIES IN MICE

Etoposide (VP 16-213), the epipodophyllotoxin derivative that is widel y used in the treatment of cancer, forms complexes with DNA-topoisomer ase type II alpha to exert its cytotoxicity. The drug was evaluated in vivo in Swiss albino mouse bone marrow cells for its ability to induc e clastogenicity and sister chromatid exchanges (SCEs). Doses of 5, 10 , 15, and 20 mg/kg body weight etoposide given intraperitoneally induc ed a dose-dependent significant increase of clastogenicity (Trend test , alpha less than or equal to 0.05). The aberrations induced were pred ominantly chromatid types. The drug shows specificity for S-phase cell s: cells harvested 6 and 12 hr posttreatment showed a significantly in creased number of damaged cells and aberrations per cell. Doses of 0.5 , 1.0, 2.5, 5.0, and 10.0 mg etoposide/kg body weight induced a dose-d ependent significant induction of SCEs (Trend test, alpha less than or equal to 0.05). The minimal effective concentration was 0.5 mg/kg bod y weight. Etoposide significantly prolonged the cell cycle time at all concentrations tested: 12-13 hr in treated animals vs. 11 hr in contr ol. The results confirm in vivo cell cycle phase specificity of the dr ug and further designate etoposide as a potent clastogen and a genotox ic agent in mice. (C) 1994 Wiley-Liss, Inc.