Toxicology Letters 104 (1999) 203 – 210
Elevation of micronuclei frequency in mouse bone marrow
treated with various doses of teniposide (VM-26)
Ganesh C. Jagetia *, R. Aruna
Department of Radiobiology, Kasturba Medical College, Manipal 576 119, India
Received 25 August 1998; received in revised form 15 October 1998; accepted 19 October 1998
Abstract
The effect of various doses (0–10 mg/kg body wt.) of teniposide (VM-26) was studied on the induction of
micronuclei at 12, 24 and 36 h post-treatment. The frequency of micronuclei (MPCE and MNCE) increased in a
dose-dependent manner up to a dose of 0.3125 mg/kg VM-26, where a peak frequency of micronuclei was observed.
A further increase in the drug dose resulted in the reduction in micronuclei frequency in comparison with 0.3125
mg/kg drug dose reaching a nadir at 10 mg/kg. However, it was significantly higher than DDW (double distilled
water) treated controls. The pattern of micronuclei induction was similar for all the post-treatment time periods. The
frequency of micronuclei also increased with scoring time and the highest frequency of micronuclei was observed at
24 h post-treatment, which declined thereafter without restoration to DDW treated control level. Conversely, the
PCE/NCE ratio registered a dose-dependent decline after treatment of mice with various doses of VM-26. A peak
decline was observed at a dose of 0.3125 mg/kg, thereafter the decline became consistently less resulting in an
elevation in the PCE/NCE ratio in comparison with 0.3125 mg/kg VM-26. © 1999 Elsevier Science Ireland Ltd. All
rights reserved.
Keywords: Mice; Teniposide; Micronuclei; PCE/NCE ratio; Bone marrow
1. Introduction
Podophyllotoxins are used in the treatment
of various malignancies. Teniposide 4-de-
methylepipodophylotoxin-4-(4,6-O-thenylidine- -
D-glucopyranoside) or VM-26 is a semisynthetic
derivative of podophyllotoxin resin. Teniposide is
an effective anticancer drug used for the treatment
of various neoplastic disorders (O’Dwyer et al.,
1984). Teniposide has been found to be active
against murine leukemias, Lewis lung carcinoma.
(Sklansky et al., 1974; Pedersen et al., 1984;
Bork et al., 1986) non-Hodgkin’s and Hodg-
kin’s Lymphoma, hematosarcomas (Mathe et al.,
1974) ovarian tumors (Van der Gaast and
* Corresponding author. Tel.: +91-8252-71200, extn.2122;
fax: +91-8252-70062.
0378-4274/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved.
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