NUMERICAL AND STRUCTURAL CHROMOSOME-ABERRATIONS INDUCED BY ETOPOSIDE (VP16) DURING OOCYTE MATURATION OF MICE - TRANSMISSION TO ONE-CELL ZYGOTES AND DAMAGE TO DICTYATE OOCYTES
Jb. Mailhes et al., NUMERICAL AND STRUCTURAL CHROMOSOME-ABERRATIONS INDUCED BY ETOPOSIDE (VP16) DURING OOCYTE MATURATION OF MICE - TRANSMISSION TO ONE-CELL ZYGOTES AND DAMAGE TO DICTYATE OOCYTES, Mutagenesis, 11(4), 1996, pp. 357-361
The antineoplastic drug etoposide (ET) inhibits topoisomerase II (topo
II) activity by forming a ternary complex (DNA-ET-topo II), This comp
lex prevents the DNA-strand-rejoining activity of topo II and may resu
lt in structural chromosome aberrations, Inhibition of topo II activit
y may also predispose cells to aneuploidy because this enzyme is neede
d for removing regions of DNA catenation prior to chromosome segregati
on, Our objectives were to study the dose response for ET-induced nume
rical and structural chromosomal aberrations in mouse one-cell zygotes
, to compare these data with those obtained from a contemporary metaph
ase II (MII) oocyte study and to evaluate the sensitivity of dictyate
oocytes to ET-induced aneuploidy, ICR female mice were superovulated a
nd injected i.p, with either 6% dimethylsulphoxide (controls) or 20, 4
0 or 60 mg/kg ET 2 h after human chorionic gonadotrophin (HCG), ICR ma
les were paired (1:1) with females immediately after treatment, After
17 h the males were removed, and after 24 h the females with a vaginal
plug were given colchicine, One-cell zygotes were harvested for cytog
enetic analysis 17 h after colchicine, The percentages of hyperploid z
ygotes were 1.1, 5.7, 13.8 and 20.7 and of zygotes with structural abe
rrations were 2.5, 16.3, 37.7 and 64.7, for control, 20, 40 and 60 mg/
kg ET respectively, The differences between each succeeding dose for b
oth structural and numerical aberrations were statistically significan
t (P < 0.01), When the ET dose response aneuploidy data from zygotes w
ere compared with similar data from a contemporary study involving met
aphase II oocytes, the frequencies of hyperploidy were greater in zygo
tes than in oocytes, We conclude that when ET is administered during t
he preovulatory phase of meiosis, it is both an aneugen and a clastoge
n in mouse one-cell zygotes.