ISSN 10227954, Russian Journal of Genetics, 2016, Vol. 52, No. 2, pp. 188–193. © Pleiades Publishing, Inc., 2016.
Original Russian Text © K.L. Pligina, A.K. Zhanataev, A.V. Kulakova, Z.V. Chaika, A.D. Durnev, 2016, published in Genetika, 2016, Vol. 52, No. 2, pp. 215–220.
The overwhelming majority of studies on the estima
tion of mutagenic and mutagenmodifying activity of
natural and synthetic compounds are conducted in in
vitro tests or in vivo tests on somatic cells [1, 2]. Studies in
germ cells are rare, which is mainly caused by the limita
tion of existing widely used techniques. The methods that
have been verified to date are complicated and laborious
and are not enough reliable due to the high probability of
false results . This determined the need for a search for
and development of new techniques of registering
mutagenic and mutagenmodifying effects in germ cells.
In particular, a new cytogenetic technique of registering
aneuploidy and structural chromosome violations in
mouse oocytes was recently suggested ; approbation
and verification in experiments with known mutagens
and antimutagens is a necessary stage of its implementa
In the present work,
acetylcysteine (ACC) was
selected as an antimutagen; it is widely used in clinical
practice as a mucolytic agent with cytoprotective
activity associated with antioxidant properties of the
preparation [4, 5]. Antimutagenic and anticarcino
genic ACC properties were demonstrated in multiple
in vivo experiments on somatic cells relative to geno
toxicants with different mechanisms of action .
Etoposide (an antitumor drug belonging to the
class of topoisomerase II inhibitors that is widely used
in clinics) was selected as a mutagen. Etoposide use is
associated with a high risk of mutagenesis and the
development of secondary tumors .
The ability of ACC to decrease lethal mutations
induced by etoposide in male mice was demonstrated
in previous studies ; no estimation effects in oocytes
was previously conducted.
The goal of the present work was to study the influ
ence of ACC on the cytogenetic effects of etoposide in
MATERIALS AND METHODS
The study was conducted on 6, 9, and 12week
old females of
C57BL/6 mice (Stolbovaya
nursery). The animals were kept in a vivarium in the
Zakusov Research Institute of Pharmacology accord
ing to the sanitary standards provided by the Labora
tory Practice Rules (Order of the Ministry of Health
and Social Development of Russian Federation from
August 23, 2004, no. 708n) with free access to water
and a balanced, briquetted, granular mixed feed from
the MEST company (Russia).
Superovulation in the mice of all experimental
groups was caused by means of an intraperitoneal
injection of 5 ME of gonadotropin of pregnant mare
serum (Folligon, Holland) and 5 ME of human chori
onic gonadotropin (hCG) (Moscow Endocrine
Plant), with a 48h interval between injections.
Etoposide at doses of 10, 20, 40, and 60 mg/kg
(EtoposideLens, Verofarm) was introduced to
females of 6weekold mice once, intraperitoneally,
simultaneously with the hCG injection. An equivalent
amount of physiological solution was introduced to
mice in the negative control group simultaneously
with the CG injection.
The experiments with modification of etoposide
effects were conducted on 6, 9, and 12weekold
Influence of Acetylcysteine on Cytogenetic Effects
of Etoposide in Mouse Oocytes
K. L. Pligina, A. K. Zhanataev, A. V. Kulakova, Z. V. Chaika, and A. D. Durnev
Zakusov Research Institute of Pharmacology, Moscow, 125315 Russia
Received April 8, 2015; in final form, May 29, 2015
—The influence of
acetylcysteine (ACC) on the cytogenetic effects of etoposide in F
C57BL/6 mice was studied. Etoposide introduced intraperitoneally in doses of 10, 20, 40, and 60 mg/kg has
a dosedependent clastogenic activity and has an aneugenic effect with the induction of mainly hypohaploid
oocytes. ACC significantly decreases the aneugenic and clastogenic activity of etoposide (20 mg/kg) in
oocytes of 6, 9, and 12weekold mice during triple introduction at a dose 200 mg/kg
. The most pro
nounced anticlastogenic ACC activity (an 80% decrease) was registered in 9weekold females; a 100%
decrease in aneugenesis was detected in 6weekold female mice.
acetylcysteine, chromosome aberrations, aneuploidy, oocytes, mice