Destabilization of human cell genome under the combined effect of radiation and ascorbic acid
The aim of this study was to investigate peculiarities of ascorbic acid effect on radiation-induced chromosomal aberrations frequency and range in the cultured peripheral blood lymphocytes (PBL) of healthy donors and cancer patients depending on doses of radiation and drug, as well as cells radiosen...
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nasplib_isofts_kiev_ua-123456789-1453742025-02-09T17:06:56Z Destabilization of human cell genome under the combined effect of radiation and ascorbic acid Domina, E.A. Pylypchuk, O.P. Mikhailenko, V.M. Original contributions The aim of this study was to investigate peculiarities of ascorbic acid effect on radiation-induced chromosomal aberrations frequency and range in the cultured peripheral blood lymphocytes (PBL) of healthy donors and cancer patients depending on doses of radiation and drug, as well as cells radiosensitivity (in vitro). Methods: Test system of human PBL, metaphase analysis of chromosomal aberrations. Cells were cultivated according to the standard procedures with some modifications. PBL culture was exposed to x-ray radiation in G0- and G2-phases of cell cycle. Immediately after the irradiation the culture was treated with ascorbic acid in concentrations of 20.0–80.0 µg/ml of blood. Results: Cell culture irradiation in low dose (0.3 Gy) and treatment with ascorbic acid in therapeutic concentration (20.0 μg/ml of blood) resulted in radioprotective effect, decreasing overall chromosome aberrations frequency as opposed to radiation effects. It has been established that post-irradiation effect of ascorbic acid upon the PBL culture in concentrations of 40.0 and 80.0 μg/ml, which exceeding therapeutic concentration value 2 and 4 times correspondingly, increased overall chromosome aberrations frequency 1.4 times compared with irradiation effect in a low dose (0.3 Gy). This bears evidence of ascorbic acid co-mutagenic activity in the range of concentrations exceeding therapeutic values. The peak of mitotic activity inhibition was observed at 2.0 Gy irradiation dose. Addition ascorbic acid in therapeutic concentration increased radiation effect this number ≈ 2 times (exceeding even intact control value). Compared with G0-phase, co-mutagenic effect of ascorbic acid in G2-phase appears earlier, starting with dose of 1.0 Gy. In the blood lymphocytes of cancer patients, the level of genetic damage was increased 1.7 times after combined treatment with low dose irradiation and ascorbic acid in comparison with irradiation alone which suggest the co-mutagenic instead of radioprotective effect of ascorbic acid. Conclusions: Genome destabilization enhancement of irradiated in vitro human somatic cells under ascorbic acid effect is due to its co-mutagenic properties. The formation of co-mutagenic effects of ascorbic acid depend on its concentration, irradiation dose and the efficiency of repair processes. Co-mutagenes may pose high carcinogenic hazard at low (above background) radiation levels. Key Words: ionizing radiation, ascorbic acid, peripheral blood lymphocytes of donors and cancer patients, chromosome aberrations, co-mutagens. 2014 Article Destabilization of human cell genome under the combined effect of radiation and ascorbic acid / E.A. Domina, O.P. Pylypchuk, V.M. Mikhailenko // Experimental Oncology. — 2014. — Т. 36, № 4. — С. 236-240. — Бібліогр.: 21 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/145374 en Experimental Oncology application/pdf Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions |
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Original contributions Original contributions Domina, E.A. Pylypchuk, O.P. Mikhailenko, V.M. Destabilization of human cell genome under the combined effect of radiation and ascorbic acid Experimental Oncology |
| description |
The aim of this study was to investigate peculiarities of ascorbic acid effect on radiation-induced chromosomal aberrations frequency and range in the cultured peripheral blood lymphocytes (PBL) of healthy donors and cancer patients depending on doses of radiation and drug, as well as cells radiosensitivity (in vitro). Methods: Test system of human PBL, metaphase analysis of chromosomal aberrations. Cells were cultivated according to the standard procedures with some modifications. PBL culture was exposed to x-ray radiation in G0- and G2-phases of cell cycle. Immediately after the irradiation the culture was treated with ascorbic acid in concentrations of 20.0–80.0 µg/ml of blood. Results: Cell culture irradiation in low dose (0.3 Gy) and treatment with ascorbic acid in therapeutic concentration (20.0 μg/ml of blood) resulted in radioprotective effect, decreasing overall chromosome aberrations frequency as opposed to radiation effects. It has been established that post-irradiation effect of ascorbic acid upon the PBL culture in concentrations of 40.0 and 80.0 μg/ml, which exceeding therapeutic concentration value 2 and 4 times correspondingly, increased overall chromosome aberrations frequency 1.4 times compared with irradiation effect in a low dose (0.3 Gy). This bears evidence of ascorbic acid co-mutagenic activity in the range of concentrations exceeding therapeutic values. The peak of mitotic activity inhibition was observed at 2.0 Gy irradiation dose. Addition ascorbic acid in therapeutic concentration increased radiation effect this number ≈ 2 times (exceeding even intact control value). Compared with G0-phase, co-mutagenic effect of ascorbic acid in G2-phase appears earlier, starting with dose of 1.0 Gy. In the blood lymphocytes of cancer patients, the level of genetic damage was increased 1.7 times after combined treatment with low dose irradiation and ascorbic acid in comparison with irradiation alone which suggest the co-mutagenic instead of radioprotective effect of ascorbic acid. Conclusions: Genome destabilization enhancement of irradiated in vitro human somatic cells under ascorbic acid effect is due to its co-mutagenic properties. The formation of co-mutagenic effects of ascorbic acid depend on its concentration, irradiation dose and the efficiency of repair processes. Co-mutagenes may pose high carcinogenic hazard at low (above background) radiation levels. Key Words: ionizing radiation, ascorbic acid, peripheral blood lymphocytes of donors and cancer patients, chromosome aberrations, co-mutagens. |
| format |
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| author |
Domina, E.A. Pylypchuk, O.P. Mikhailenko, V.M. |
| author_facet |
Domina, E.A. Pylypchuk, O.P. Mikhailenko, V.M. |
| author_sort |
Domina, E.A. |
| title |
Destabilization of human cell genome under the combined effect of radiation and ascorbic acid |
| title_short |
Destabilization of human cell genome under the combined effect of radiation and ascorbic acid |
| title_full |
Destabilization of human cell genome under the combined effect of radiation and ascorbic acid |
| title_fullStr |
Destabilization of human cell genome under the combined effect of radiation and ascorbic acid |
| title_full_unstemmed |
Destabilization of human cell genome under the combined effect of radiation and ascorbic acid |
| title_sort |
destabilization of human cell genome under the combined effect of radiation and ascorbic acid |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2014 |
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Original contributions |
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https://nasplib.isofts.kiev.ua/handle/123456789/145374 |
| citation_txt |
Destabilization of human cell genome under the combined effect of radiation and ascorbic acid / E.A. Domina, O.P. Pylypchuk, V.M. Mikhailenko // Experimental Oncology. — 2014. — Т. 36, № 4. — С. 236-240. — Бібліогр.: 21 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT dominaea destabilizationofhumancellgenomeunderthecombinedeffectofradiationandascorbicacid AT pylypchukop destabilizationofhumancellgenomeunderthecombinedeffectofradiationandascorbicacid AT mikhailenkovm destabilizationofhumancellgenomeunderthecombinedeffectofradiationandascorbicacid |
| first_indexed |
2025-11-28T09:42:46Z |
| last_indexed |
2025-11-28T09:42:46Z |
| _version_ |
1850026722813018112 |
| fulltext |
236 Experimental Oncology 36, 236–240, 2014 (December)
DESTABILIZATION OF HUMAN CELL GENOME UNDER
THE COMBINED EFFECT OF RADIATION AND ASCORBIC ACID
E.A. Domina, O.P. Pylypchuk, V.M. Mikhailenko
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Siences of Ukraine, Kyiv 03022, Ukraine
The aim of this study was to investigate peculiarities of ascorbic acid effect on radiation-induced chromosomal aberrations frequency and
range in the cultured peripheral blood lymphocytes (PBL) of healthy donors and cancer patients depending on doses of radiation and drug,
as well as cells radiosensitivity (in vitro). Methods: Test system of human PBL, metaphase analysis of chromosomal aberrations. Cells
were cultivated according to the standard procedures with some modifications. PBL culture was exposed to x-ray radiation in G0-
and G2-phases of cell cycle. Immediately after the irradiation the culture was treated with ascorbic acid in concentrations
of 20.0–80.0 μg/ml of blood. Results: Cell culture irradiation in low dose (0.3 Gy) and treatment with ascorbic acid in therapeutic
concentration (20.0 μg/ml of blood) resulted in radioprotective effect, decreasing overall chromosome aberrations frequency as op-
posed to radiation effects. It has been established that post-irradiation effect of ascorbic acid upon the PBL culture in concentrations
of 40.0 and 80.0 μg/ml, which exceeding therapeutic concentration value 2 and 4 times correspondingly, increased overall chromosome
aberrations frequency 1.4 times compared with irradiation effect in a low dose (0.3 Gy). This bears evidence of ascorbic acid co-muta-
genic activity in the range of concentrations exceeding therapeutic values. The peak of mitotic activity inhibition was observed at 2.0 Gy ir-
radiation dose. Addition ascorbic acid in therapeutic concentration increased radiation effect this number ≈ 2 times (exceeding even intact
control value). Compared with G0-phase, co-mutagenic effect of ascorbic acid in G2-phase appears earlier, starting with dose of 1.0 Gy.
In the blood lymphocytes of cancer patients, the level of genetic damage was increased 1.7 times after combined treatment with low dose
irradiation and ascorbic acid in comparison with irradiation alone which suggest the co-mutagenic instead of radioprotective effect
of ascorbic acid. Conclusions: Genome destabilization enhancement of irradiated in vitro human somatic cells under ascorbic acid effect
is due to its co-mutagenic properties. The formation of co-mutagenic effects of ascorbic acid depend on its concentration, irradiation dose
and the efficiency of repair processes. Co-mutagenes may pose high carcinogenic hazard at low (above background) radiation levels.
Key Words: ionizing radiation, ascorbic acid, peripheral blood lymphocytes of donors and cancer patients, chromosome aberra-
tions, co-mutagens.
One of the important components of primary radio-
genic cancer prevention is taking into account effect
of co-mutagens on humans [1]. These are compounds
that, while not having mutagenic properties of their own,
can significantly modify (enhance) effects of known
mutagens of chemical nature. Drugs with co-mutagenic
properties remain understudied, since having no own
mutagenic activity, they are not detected at geno-
toxic screening [2, 3]. To this day, no researches are
conducted, aimed at study of co-mutagens impact
on radiogenic, including carcinogenic, effects formation
in human cells under the impact of low radiation doses.
Possible co-mutagenic effects of some common drugs,
for instance, ascorbic acid (AA), which is designated
as “signal molecule causing specific activity in cells”,
are of high scientific and practical interest [4]. In series
of studies, ambiguous effect of AA on human cells has
been revealed [5–10]. It has been established that
as opposed to the animals, AA is not produced in human
organism, and its food deficiency contributes to the de-
velopment of gastric cancer, cancer of esophagus,
oral cavity, cervix [6]. There is a contradictory view that
vitamins, including AA, are impractical to use for carci-
nogenic risk [5]. Data on antitumor effect of AA at breast
cancer [7], gastric cancer [8], prostate cancer [9] and
other tumor localizations have been obtained. Re-
searchers fairly state that interpretation of data received
on experimental animals on radioprotective and co-
mutagenic effects of some drugs, including vitamins-
antioxidants, is “wrong to extrapolate to human” [11].
Data on AA impact nature is not always confirmed even
in methodically close studies [2].
Due to existing environmental situation in post-
Chernobyl period, probabilistic development of car-
cinogenic effects of low dose ionizing radiation (IR)
and oncogenic hazard of increased level of chromo-
some changes in cell population, study of AA effect
on formation of radiation-induced instability of human
somatic cells genome is relevant.
Application of test-system of human peripheral
blood lymphocytes (PBL), which are the most radiosen-
sitive somatic cells [12], allows to model hypothetic situ-
ations under combined irradiation and drugs effect with
possible co-mutagenic activity on chromosome level.
It is expected that the formation of AA co-mutage-
nic effects may be specific, not only depending on its
concentration or radiation dose, but differ signifi-
cantly in healthy donors and cancer patients cells due
to the inhibitory effect of the pathological process
on repair processes efficiency.
In presented study, peculiarities of AA effect on ra-
diation-induced chromosomal aberrations frequency
and range in PBL culture of donors and cancer patients
depending on radiation dose and drug concentration,
as well as cells radiosensitivity, have been studied
(research in vitro).
Submitted: July 03, 2014.
*Correspondence: E-mail: lena.pylypchuk@ukr.net
Abbreviations used: AA — ascorbic acid; IR — ionizing radiation;
PBL — peripheral blood lymphocytes.
Exp Oncol 2014
36, 4, 236–240
Experimental Oncology 36, 236–240, 2014 (December) 237
MATERIALS AND METHODS
Healthy donors and cancer patients (endometrial
cancer) (20 observations) venous blood has been cul-
tivated by semi-micro method with some modifications
during 52 h [13]. This study was guided by regulations
of Helsinki Declaration of the World Medical Association
(2008), which provides informed consent of donors for
participation in study. Study algorithm is represented
in Fig. 1. Cells were incubated in RPMI 1640 medium
(“Biowest”, France), containing 0.1 μg/ml PHA (M form,
“Gibco-Invitrogen”, USA) for 52 h (last 3 h with col-
cemid (“Biowest”, France). PBL culture was exposed
to radiation in G0- and G2-phases of cell cycle (for 0 and
46 h of cells incubation correspondingly) on X-ray unit
“RUM-17”. The irradiation conditions: current was
10 mA, voltage — 200 kV, Cu filter (0.5 mm), dose
rate — 0.89 Gy/min, studied doses range 0.3–2.0 Gy. In-
troduced in PBL culture right after irradiation at concen-
trations 20.0–80.0 μg/ml of blood that corresponded
with therapeutic concentration, and also 2 and 4 times
exceeding it, AA has been used as radiation effect modi-
fier. To arrest dividing lymphocytes in metaphase, col-
cemid was added 3 h prior to the harvest. Preparations
were made according to the standard procedure. Slides
were stained with 5% Giemsa solution (Gibco, USA). All
slides were coded and scored blindly at 100 × magnifi-
cation under oil immersion. Metaphase analysis of cells
was carried out in the first postradiation mitosis [14].
On each observation, an average 200–300 metaphases
have been analyzed. Value mitotic index has been used
as index of lymphocytes proliferative activity for which
the amount of cells at mitosis stage was determined.
Statistical analysis of obtained results was performed
using of descriptive methods, and Student’s t-criterion
(program Excel) [15].
FHA
FHA
IR AA
IR AA K F
K F
Ph
as
es
o
f m
ito
tic
c
yc
le
G0
G2
0
0
49 52
4946 52
Incubation time (hours)
M
et
ap
ha
si
c
an
al
ys
is
Fig. 1. A study algorithm of AA effect on the irradiated PBL
of donors and cancer patients chromosomal level. FHA — mi-
togen; K — colcemid; F — cell fixation; IR — ionizing radiation;
AA — ascorbic acid
RESULTS AND DISCUSSION
AA in the studied concentrat ions range
(20.0–80.0 μg/ml of blood) does not impact of chro-
mosome aberrations spontaneous level in lympho-
cytes of donors and corresponds to mean population
values (2.0 ± 0.86 per 100 metaphases). Results
fit the data of study [16], in which lack of vitamins-
antioxidants impact on spontaneous mutation process
in human lymphocytes has been demonstrated.
When analyzing frequency of chromosome dama-
ges, induced by PBL irradiation in G0-phase of cell cycle
(in dose range 0.3–2.0 Gy), and post-radiation impact
of AA (in concentrations range of 20.0–80.0 μg/ml),
modifying effect of this drug was ambiguous (Fig. 2).
0
5
10
15
20
25
0 0.3 0.5 1.0 2.0
Exposure to radiation, Gy
O
ve
ra
ll
fre
qu
en
cy
o
f c
hr
om
os
om
e
ab
er
ra
tio
ns
p
er
1
00
m
et
ap
ha
se
s Control
Control + AA (20.0 μg/ml of blood)
PBL irradiation in G0-phase of cell cycle
PBL irradiation in G0-phase of cell cycle +
AA (20.0 μg/ml of blood)
Fig. 2. Overall frequency of chromosome aberrations in PBL
culture at combined effect of radiation and AA in therapeutic
concentration of 20.0 μg/ml of blood
Combined with IR in low dose (0.3 Gy), AA in thera-
peutic concentration (20.0 μg/ml of blood) shows
radioprotective effect, which manifests in overall chro-
mosome aberrations frequency decrease compared
to effect of radiation alone (see Fig. 2). However,
PBL irradiation in relatively high dose (2.0 Gy), under
the impact of AA in the same concentration, shows
potentiating of this effect — increase of chromosome
aberrations overall frequency in ≈ 1.4 times that point
to the co-mutagenic properties of the drug. Observed
potentiating of radiation-induced cytogenetic effect
occurs due to radial markers — dicentric chromo-
somes (10/100 metaphases compared with irradia-
tion — 5/100 metaphases) (Fig. 3).
Fig. 3. Microphoto of a metaphase plate with dicentric chromo-
some and pair fragment specified by the arrow (× 100)
Since formation of exchange aberrations — dicen-
trics, requires local double breaks of chromosomes,
resulted due to irradiation, increased aberrations of such
type output under additional AA effect can be interpreted
as evidence of primary radial damages realization en-
hancement under the effect of studied drug.
Modification cytogenetic effects of low dose IR un-
der the AA effect in concentrations exceeding thera-
peutic values deserves special attention. It was estab-
238 Experimental Oncology 36, 236–240, 2014 (December)
lished that post-radial effect of AA on the PBL culture
in concentrations of 40.0 and 80.0 μg/ml, exceeding
the value of therapeutic concentration in 2 and 4 times
correspondingly, increases overall chromosome aber-
rations frequency as opposed to effect of irradiation
in low dose (0.3 Gy) in 1.4 times (Fig. 4). This may point
to co-mutagenic activity of AA in the concentrations
range exceeding therapeutic values. Since irradia-
tion in low doses along with chromosome breaks may
induce pre-mutative potential changes in the latter,
additional effect of co-mutagens in high concentra-
tion may contribute to their realization in structural
rearrangement of chromosomes, due to suppression
of reparation enzymes included [17, 18]. Thus, AA anti-
oxidant depending on concentration at cells irradiation
in low doses can manifest both radioprotective and
co-mutagenic effects.
0
5
10
15
20
1 2 3 4 5
Low doses of radiation (0.3 Gy)
O
ve
ra
ll
fre
qu
en
cy
o
f c
hr
om
os
om
e
ab
er
ra
tio
ns
p
er
1
00
m
et
ap
ha
se
s
Control
PBL irradiation in G0-phase of cell cycle
PBL irradiation in G0-phase of cell cycle + AA
(20.0 μg/ml of blood)
PBL irradiation in G0-phase of cell cycle + AA
(40.0 μg/ml of blood)
PBL irradiation in G0-phase of cell
cycle + AA (80.0 μg/ml of blood)
Fig. 4. Overall frequency of chromosome aberrations in PBL
culture under combined effect of low doses of radiation (0.3 Gy)
and AA in the range of concentrations (20.0–80.0 μg/ml of blood)
Thus it can be generalized that formation of some
drugs co-mutagenic effects in irradiated human cells
depends on both the concentration and radiation
dose. Considering carcinogenic hazard of low radiation
doses the greatest threat co-mutagenesis can pose
is at radiation levels effect without background. Forma-
tion of AA co-mutagenic effect depending on irradiation
dose is showed on Fig 5. Applying AA in concentration
of 20.0 μg/ml after cell irradiation in dose of 0.3 Gy, led
to decrease of chromosome aberrations frequency
at culture irradiation in low doses to 6.0 ± 1.4 per
100 metaphases as opposed to 9.0 ± 0.86 dose effect,
which confirms radioprotective properties of AA. Using
AA in concentrations exceeding therapeutic dose value
to in 4 times (40.0–80.0 μg/ml), shows co-mutagenic
properties, increasing overall chromosome aberrations
frequency compared with 0.3 Gy dose ≈ 1.4 times. Upon
irradiating cells, co-mutagenic properties of AA are
manifested at its concentrations exceeding therapeu-
tic value. At exposure of cells to radiation in relatively
high dose (2.0 Gy), co-mutagenic effect of AA is kept
regadles of changes in concentrations, increasing on av-
erage frequency of chromosomal aberrations 1.4 times
due to chromosome type aberrations. This results are
confirmed by the study [19] data, according to which
in certain conditions of experiment, AA shows prooxidant
activity and in such way provides oxidative cell damage.
0
5
10
15
20
25
0.3 2.0Exposure to radiation, Gy
O
ve
ra
ll
fre
qu
en
cy
o
f c
hr
om
os
om
e
ab
er
ra
tio
ns
p
er
1
00
m
et
ap
ha
se
s
Control
PBL irradiation in G0-phase of cell cycle
PBL irradiation in G0-phase of cell cycle +
AA (20.0 μg/ml of blood)
PBL irradiation in G0-phase of cell
cycle + AA (80.0 μg/ml of blood)
Fig. 5. Overall frequency of chromosome aberrations in PBL
culture under combined effect of radiation (0.3–2.0 Gy) and
AA in the range of concentrations (20.0–80.0 μg/ml of blood)
It is known that low capability of lymphocytes to sti-
m u lation by different mutagens may be the evidence
of presence and/or induction of genetic disorders
in cells, depression of T-lymphocytes, changes in their
functional state, development of malignant neoplasms
in individuals exposed to radiation [20]. Analysis of PBL
mitotic activity under the conditions of combined ir-
radiation (0.3–2.0 Gy) and AA (20.0 μg/ml) effect
in G0-phase of cell cycle showed the following (Fig. 6).
Most pronounced suppression of cells mitotic activity
was noted at irradiation in 2.0 Gy dose, and additional
AA effect in therapeutic concentration, on the contrary,
increased it ≈ 2 times (exceeding even intact control
value). We suppose that this effect is due to “removal”
of radiation-induced block (delay of mitosis) under
the effect of this drug which shortens time of primary
damages reparation. It is confirmed by increase of total
chromosome aberrations frequency in these experi-
mental conditions (see Fig. 2).
0
10
20
30
40
50
60
70
80
Control 0.3 0.5 1.0 2.0
Exposure to radiation, Gy
M
ito
tic
in
de
x,
‰
Control
Control + AA (20.0 μg/ml of blood)
PBL irradiation in G0-phase of cell cycle
PBL irradiation in G0-phase of cell cycle +
AA (20.0 μg/ml of blood)
Fig. 6. Combined effect of IR (0.3–2.0 Gy) and AA (20.0 μg/ml)
upon PBL mitotic activity
According to the paradigms of radiobiology, radio-
sensitivity of chromosomes is differentiated depending
on phase of mitotic cycle owing to the different effec-
tiveness of repair processes [21]. Study of this drug
co-mutagenic activity depending on cells radiosensi-
tivity presents certain scientific interest. In this regard
similar experiments in the most radiosensitive G2-phase
of lymphocytes cell cycle were conducted in culture
(see Fig. 1). Analysis of registered chromosome damage
at PBL irradiation during radiosensitive G2-phase showed
that chromatic type aberrations, represented by deletions
and exchanges, prevailed in the range (Fig. 7).
Experimental Oncology 36, 236–240, 2014 (December) 239
Fig. 7. Microphoto of a metaphase plate with deletion, indicated
by the arrow (× 100)
Cytogenetic analysis showed that at PBL irradiation
with a dose of 0.3 Gy during G2-phase of the cell cycle
the AA drug has insignificant radioprotective effect
in therapeutic concentrations (Fig. 8).
0
5
10
15
20
25
0 0.3 1.0 2.0
Exposure to radiation, Gy
O
ve
ra
ll
fre
qu
en
cy
o
f c
hr
om
os
om
e
ab
er
ra
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ns
p
er
1
00
m
et
ap
ha
se
s
Control
Control + AA (20.0 μg/ml of blood)
PBL irradiation in G2-phase of cell cycle
PBL irradiation in G2-phase of cell
cycle + AA (20.0 μg/ml of blood)
Fig. 8. Overall frequency of chromosome aberrations in PBL
culture at combined effect of radiation and AA in therapeutic
concentration of 20.0 μg/ml of blood
Compared with G0-phase, co-mutagenic ef-
fect of AA in G2-phase appears earlier, starting from
1.0 Gy dose (18.0 ± 1.4 and 12.0 ± 1.1, correspondingly;
meaning potentiating of effect ≈ 1,5 times) due to higher
cells radiosensitivity in this phase of cell cycle (see Fig. 2, 8).
Equally important are the results obtained with AA ef-
fect at the chromosomal level of cancer patients PBL
(Fig. 9). It is shown that AA concentrations (20.0 and
80.0 μg/ml) did not cause any increase in the cells with
chromosome aberrations as opposed to the sponta-
neous level of chromosome aberrations (7.0 ± 0.8)
in the patients non-irradiated PBL. However, the com-
bined action of low IR doses (0.3 Gy) and AА (20.0 and
80.0 μg/ml of blood) in cancer patients lymphocytes
display different co-mutagenic effects then the results
obtained in similar experimental conditions on the donor
cells. Combined with irradiation AA shows co-mutage nic
effect in both drug concentrations (see Fig. 4, 9).
Scientific novelty of this findings lies in the fact
that аt combined in vitro effect of low dose irradiation
and AA in the therapeutic concentration in the blood
lymphocytes of cancer patients there is an increase
of genetic damage frequency 1.7 times as opposed
to the irradiation effect (meaning the co-mutagenic
instead of radioprotective effect of AA appears).
The results come as solid proof of the repair processes
dominant role in some drugs co-mutagenic activity
display, in this case, at the combined effect of radiation
(additional) radiation levels and AА.
0
5
10
15
20
25
1 2 3 4
Low doses of radiation (0.3 Gy)
O
ve
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o
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ap
ha
se
s
Control
PBL irradiation in G0-phase of cell cycle
PBL irradiation in G0-phase of cell
cycle + AA (20.0 μg/ml of blood)
PBL irradiation in G0-phase
of cell cycle + AA
(80.0 μg/ml of blood)
Fig. 9. Overall frequency of chromosome aberrations in cancer
patients PBL culture under combined effect of low irradiation
doses (0.3 Gy) and AA in the range of concentrations (20.0;
80.0 μg/ml of blood)
Thus, based on cytogenetic studies, it has been
established that co-mutagenic properties of AA can
appear in irradiated cells depending on its concentra-
tion, value of IR dose and cells radiosensetivity. High
co-mutagens concentrations potentiate damaging
effect of low dose IR. We believe that individuals with
high sensitivity to radiation and being under contact
with sources of IR need an individual approach to use
drugs with co-mutagenic activity in medical purposes.
CONCLUSIONS
Genome destabilization enhancement of irradiated
in vitro human somatic cells under AA effect is due
to its co-mutagenic properties. The formation of co-
mutagenic effects of AA depend on its concentration,
irradiation dose and the efficiency of repair processes.
Co-mutagenes may pose high carcinogenic hazard
at low (above background) radiation levels.
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