The ability of
topoisomerase II inhibitor,
teniposide, to induce
aneuploidy and meiotic delay in somatic and germinal cells of male mice was investigated by fluorescence in situ hybridisation (FISH) assay using labelled
DNA probes and
5-bromo-2'-deoxyuridine (
BrdU) incorporation assay, respectively.
Colchicine and
mitomycin C were used as a positive control
aneugen and
clastogen, respectively, and these compounds produced the expected responses. Using FISH assay with centromeric and telomeric
DNA probes for erythrocyte, micronuclei (MN) showed that
teniposide is not only clastogenic but also aneugenic in somatic cells in vivo. The assay also showed that chromosomes can be enclosed in the MN before and after centromere separation. By using the
BrdU incorporation assay, it could be shown that the meiotic delay caused by
teniposide in germ cells was ∼48 h. Disomic and diploid sperms were shown in epididymal sperm hybridised with
DNA probes specific for chromosomes 8, X and Y after
teniposide treatment. The prevalence of autodiploid (XX88 and YY88) sperm and disomic XX8 or YY8 sperm indicates that the second meiotic division was more sensitive to
teniposide than the first meiotic division. The results also suggest that earlier prophase stages contribute relatively less to
teniposide-induced
aneuploidy. Both the clastogenic and the aneugenic potential of
teniposide can give rise to the development of secondary tumours and abnormal reproductive outcomes in cured
cancer patients and medical personnel exposing to
drug regimens that include
teniposide. Thus, genetic counselling of these patients should take place before the start of
chemotherapy and should take the present results into consideration.