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Etoposide (VP‐16): Cytogenetic studies in mice
Author(s) -
Agarwal Kalpana,
Mukherjee Anita,
Sen Soumitra
Publication year - 1994
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850230307
Subject(s) - clastogen , etoposide , in vivo , sister chromatid exchange , pharmacology , genotoxicity , biology , bone marrow , mutagen , toxicity , podophyllotoxin , carcinogen , chemistry , in vitro , chemotherapy , immunology , biochemistry , genetics , stereochemistry , organic chemistry
Etoposide (VP 16‐213), the epipodophyllotoxin derivative that is widely used in the treatment of cancer, forms complexes with DNA‐topoisomerase type llα to exert its cytotoxicity. The drug was evaluated in vivo in Swiss albino mouse bone marrow cells for its ability to induce clastogenicity and sister chromatid exchanges (SCEs). Doses of 5, 10, 15, and 20 mg/kg body weight etoposide given intraperitoneally induced a dose‐dependent significant increase of clastogenicity (Trend test, α ≦ 0.05). The aberrations induced were predominanty chromatid types. The drug shows specificity for S‐phase cells: cells harvested 6 and 12 hr posttreatment showed a significantly increased 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‐dependent significant induction of SCEs (Trend test, α ≦ 0.05). The minimal effective concentration was 0.5 mg/kg body weight. Etoposide significantly prolonged the cell cycle time at all concentrations tested: 12‐13 hr in treated animals vs. 11 hr in control. The results confirm in vivo cell cycle phase specificity of the drug and further designate etoposide as a potent clastogen and a genotoxic agent in mice. © 1994 Wiley‐Liss, Inc.