On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy
Ion beam therapy is one of the most effective methods in treatment of cancer diseases. But up to nowadays, the mechanism of action of heavy ions on cancer cells has not been determined yet. Study of water fragmentation processes during ion beam therapy shows that, among different oxygen species, t...
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Видавничий дім "Академперіодика" НАН України
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irk-123456789-1581282019-07-19T01:25:32Z On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy Zdorevskyi, O.O. Piatnytskyi, D.V. Volkov, S.N. Біофізика Ion beam therapy is one of the most effective methods in treatment of cancer diseases. But up to nowadays, the mechanism of action of heavy ions on cancer cells has not been determined yet. Study of water fragmentation processes during ion beam therapy shows that, among different oxygen species, the significant amount of hydrogen peroxide molecules (H₂O₂) occurs in the сell medium. In the present work, the competitive interaction of H₂O₂ and H₂O molecules with specific DNA recognition sites is studied. Interaction energies of complexes consisting of nucleic bases (adenine, thymine, guanine, and cytosine) together with hydrogen peroxide and water molecules are calculated, using the method of atom-atom potential functions and density functional theory. The atomic groups of nuc leic bases that are more energetically favorable to be bound by hydrogen peroxide rather than by water molecule are found. Formation of such complexes can block the process of DNA replication on different stages and can be one of the mechanisms of ion beam action on cancer cells. Іонна терапія є одним з найефективніших методів лікування ракових захворювань. Але до цього часу механізм дії важких іонів на ракові клітини не визначений. Вивчення процесів фрагментації води під час іонної терапії показує, що серед великої кількості різних фрагментів у середовищі клітини утворюється значна концентрація молекул пероксиду водню (H₂O₂). У роботі наведено результати дослідження конкурентної взаємодії молекул H₂O₂ та H₂O із центрами специфічного розпізнавання ДНК. Енергії взаємодії комплексів, що складаються з нуклеїнових основ (аденін, тимін, гуанін і цитозин) разом з молекулами пероксиду водню і води, обчислені із застосуванням методу атом-атомних потенціальних функцій і теорії функціонала густини. Знайдено атомні групи нуклеїнових основ, які є більш енергетично вигідними для зв’язування з молекулами пероксиду водню, ніж з молекулами води. Утворення таких комплексів може блокувати процес реплікації ДНК на різних етапах і може бути одним з механізмів дії високоенергетичних іонів на ракові клітини. Ионная терапия является одним из наиболее эффективных методов лечения раковых заболеваний. Но до настоящего времени механизм действия тяжелых ионов на раковые клетки не установлен. Изучение процессов фрагментации воды при ионной терапии показывает, что среди большого количества различных фрагментов в клеточной среде образуется значительная концентрация молекул пероксида водорода (H₂O₂). В работе приведены результаты изучения конкурентного взаимодействия молекул H₂O₂ и H₂O с центрами специфического узнавания ДНК. Энергии взаимодействия комплексов, состоящих из нуклеиновых оснований (аденин, тимин, гуанин и цитозин) вместе с молекулами пероксида водорода и воды, рассчитаны с использованием метода атом-атомных потенциальных функций и теории функционала плотности. Найдены атомные группы нуклеиновых оснований, с которыми молекула пероксида водорода связывается значительно энергетически выгоднее, чем молекула воды. Образование таких комплексов может блокировать процесс репликации ДНК на разных стадиях и может быть одним из механизмов воздействия высокоэнергетических ионов на раковые клетки. 2019 Article On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy / O.O. Zdorevskyi, D.V. Piatnytskyi, S.N. Volkov // Доповіді Національної академії наук України. — 2019. — № 6. — С. 82-89. — Бібліогр.: 15 назв. — англ. 1025-6415 DOI: doi.org/10.15407/dopovidi2019.06.082 http://dspace.nbuv.gov.ua/handle/123456789/158128 539.199+577.323 en Доповіді НАН України Видавничий дім "Академперіодика" НАН України |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| language |
English |
| topic |
Біофізика Біофізика |
| spellingShingle |
Біофізика Біофізика Zdorevskyi, O.O. Piatnytskyi, D.V. Volkov, S.N. On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy Доповіді НАН України |
| description |
Ion beam therapy is one of the most effective methods in treatment of cancer diseases. But up to nowadays, the
mechanism of action of heavy ions on cancer cells has not been determined yet. Study of water fragmentation processes
during ion beam therapy shows that, among different oxygen species, the significant amount of hydrogen
peroxide molecules (H₂O₂) occurs in the сell medium. In the present work, the competitive interaction of H₂O₂ and
H₂O molecules with specific DNA recognition sites is studied. Interaction energies of complexes consisting of nucleic
bases (adenine, thymine, guanine, and cytosine) together with hydrogen peroxide and water molecules are calculated,
using the method of atom-atom potential functions and density functional theory. The atomic groups of nuc leic
bases that are more energetically favorable to be bound by hydrogen peroxide rather than by water molecule are
found. Formation of such complexes can block the process of DNA replication on different stages and can be one of
the mechanisms of ion beam action on cancer cells. |
| format |
Article |
| author |
Zdorevskyi, O.O. Piatnytskyi, D.V. Volkov, S.N. |
| author_facet |
Zdorevskyi, O.O. Piatnytskyi, D.V. Volkov, S.N. |
| author_sort |
Zdorevskyi, O.O. |
| title |
On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy |
| title_short |
On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy |
| title_full |
On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy |
| title_fullStr |
On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy |
| title_full_unstemmed |
On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy |
| title_sort |
on a possibility of the blocking of dna specific recognition sites by hydrogen peroxide molecules during ion beam therapy |
| publisher |
Видавничий дім "Академперіодика" НАН України |
| publishDate |
2019 |
| topic_facet |
Біофізика |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/158128 |
| citation_txt |
On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy / O.O. Zdorevskyi, D.V. Piatnytskyi, S.N. Volkov // Доповіді Національної академії наук України. — 2019. — № 6. — С. 82-89. — Бібліогр.: 15 назв. — англ. |
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Доповіді НАН України |
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2025-07-14T10:38:06Z |
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82 ISSN 1025-6415. Dopov. Nac. akad. nauk Ukr. 2019. № 6
ОПОВІДІ
НАЦІОНАЛЬНОЇ
АКАДЕМІЇ НАУК
УКРАЇНИ
© O.O. Zdorevskyi, D.V. Piatnytskyi, S. N. Volkov, 2019
1. Introduction. One of the most important problems of humanity nowadays is the treatment of
cancer diseases. Current statistics shows that, over recent decades, the number of new drugs to
fight cancer has grown rapidly, while the mortality from oncological diseases is almost unchanged.
That is why the different alternatives to pharmacological approaches in the cancer treatment are
widely used. One of the most effective methods is radiation therapy. In this approach, the living
tissue of the patient is exposed to a certain type of ionizing radiation (X-rays, gamma rays, pho-
tons), but the effectiveness of these approaches remains still insufficient. During the recent time,
the more and more attention is paid to ion beam therapy. In contrast to other types of ionizing
ra diation, heavy ions almost do not interact with the molecules of the medium and transfer the
most amount of their energy at the end of their track, where the tumor is localized. This effect has
been known in nuclear physics for many years (Bragg’s peak [1]), but began to be used in medi-
cine only in the last decades. The main advantage of heavy-ions therapy over other types of radia-
tion is the accurate and targeted tumor treatment without significant damage to the rest of the
patient’s body.
doi: https://doi.org/10.15407/dopovidi2019.06.082
UDC 539.199+577.323
O.O. Zdorevskyi, D.V. Piatnytskyi, S. N. Volkov
Bogolyubov Institute for Theoretical Physics of the NAS of Ukraine, Kiev
E-mail: snvolkov@bitp.kiev.ua
On a possibility of the blocking of DNA specific recognition sites
by hydrogen peroxide molecules during ion beam therapy
Presented by Academician of the NAS of Ukraine A.G. Zagorodny
Ion beam therapy is one of the most effective methods in treatment of cancer diseases. But up to nowadays, the
mechanism of action of heavy ions on cancer cells has not been determined yet. Study of water fragmentation pro-
cesses during ion beam therapy shows that, among different oxygen species, the significant amount of hydrogen
peroxide molecules (H2O2) occurs in the сell medium. In the present work, the competitive interaction of H2O2 and
H2O molecules with specific DNA recognition sites is studied. Interaction energies of complexes consisting of nucleic
bases (adenine, thymine, guanine, and cytosine) together with hydrogen peroxide and water molecules are calcu-
lated, using the method of atom-atom potential functions and density functional theory. The atomic groups of nuc leic
bases that are more energetically favorable to be bound by hydrogen peroxide rather than by water molecule are
found. Formation of such complexes can block the process of DNA replication on different stages and can be one of
the mechanisms of ion beam action on cancer cells.
Keywords: DNA nucleic bases, hydrogen peroxide, cancer therapy.
БІОФІЗИКА
83ISSN 1025-6415. Допов. Нац. акад. наук Укр. 2019. № 6
On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules...
When ionizing radiation passes through the living tissue, different chemical reactions ta ke place.
As a result, a variety of species occurs in the water medium. Among them are free radicals, secondary
electrons, ions, as well as molecular products (H2 and H2O2). According to the multiscale ap-
proach of ion beam therapy [2], the main factor that deactivates cancer cells is the da mages to the
structure of their DNA called DNA strand breaks. However, due to the DNA repa ration mecha-
nisms, the living cell can effectively treat the lesions of its double helix. So, the question about the
biological mechanism of deactivation of cancer cells in ion beam therapy still remains open [3].
Simulations of the water radiolysis process [4] shows that, on the scale of biological lifeti mes
(∼1 μsec), the largest concentration among all the products is revealed by hydrogen peroxide
molecules (H2O2), but their role in the ion therapy of cells remains unexplained yet. In our pa-
per [5], it was proposed a hypothesis that hydrogen peroxide can create stable complexes with
DNA active sites and block, in this way, the DNA replication processes. Under physiological
conditions, these sites are surrounded by water molecules. But, due to an increase of the con-
centration of H2O2, these molecules should compete with water molecules for the binding with
DNA sites. Therefore, it is important to understand whether hydrogen peroxide molecules can
interact with active DNA recognition sites stronger than water molecules, thus blocking the pro-
cesses of genetic information transfer.
In work [5], the interaction of hydrogen peroxide molecules with centers of non-specific pro-
tein-nucleic recognition, DNA phosphate groups (PO4), was studied. It was shown that H2O2
molecule can form sufficiently stable complexes with DNA PO4 groups and counterions, and
block the protein-nucleic recognition process. In the present paper, we consider the interaction
of H2O2 and H2O molecules with specific DNA recognition sites — atomic groups of adenine,
thymine, guanine, and cytosine (A, T, G, and C) nucleic bases — to determine if they can form
stable complexes.
The next section will describe our calculation methods. In Sec. 3, a comparative analysis of
the stability of the complexes consisting of H2O2 and H2O molecules with nucleic base (adenine,
thymine, guanine, or cytosine) will be performed. In Sec. 4, it will be discussed how our results
can lead to the understanding of the mechanism of blocking of the genetic information transfer
processes.
2. Materials and methods. For the analysis of the interaction energy and structure of the
investigated molecular complexes, two computational approaches are used — the method of clas-
sical atom-atom potential functions (AAPF) and the method of quantum-chemical calculations
based on density functional theory with B3LYP functional. In this section, we will briefly de-
scribe these two approaches.
2.1. Atom-atom potential function method. The atom-atom potential function method is de-
scribed in details in work [6]. In addition, when considering the hydrogen bond interaction be-
tween atoms i and j situated on a distance rij between each other,
(10) (10)
10 12
( ) [ ]cos ,ij ij
HB ij
ij ij
A B
E r
r r
= − + ϕ (1)
we take angle ϕ into account — the angle of the hydrogen bond. For example, when the hydro-
gen bond is O—H . . . N, then ϕ is an angle between the lines of covalent bond (O—H) and the
84 ISSN 1025-6415. Dopov. Nac. akad. nauk Ukr. 2019. № 6
O.O. Zdorevskyi, D.V. Piatnytskyi, S. N. Volkov
hydrogen bond (H . . . N). In (1), cosϕ means that the more the hydrogen bond is bent, the less
the interaction energy is.
The Coulomb interaction is described by the electrostatic potential:
Coul
0
1
( ) ,
4 ( )
i j
ij
ij ij
q q
E r
r r
=
πε ε (2)
where qi and qj are the charges of the atoms i and j located at a distance rij, ε0 is the vacuum per-
mittivity, and ε(r) is the dielectric permittivity of the medium.
The charges qi, qj for nucleic bases were taken from works [7, 8]. The charges of H2O and
H2O2 molecules were calculated from the condition that the dipole moment of a water molecule
should be equal to dH2O = 1.86 D, and that of a hydrogen peroxide molecule dH2O2
= 2.10 D [5].
Hence, for an H2O molecule, we obtain the charges qH = 0.33e, qO = –0.66e, and, accordingly, for
H2O2, qH = 0.41e; qO = –0.41e. The values of charges on the atoms of an H2O2 molecule are in
good agreement with charges obtained in work [9]. Since DNA in a living cell is situated in a
water-ion solution, the interacting atoms are screened by water molecules. This leads to a weak-
ening of the Coulomb interaction. Thus, the more effective accounting of the Coulomb inter-
action can be achieved using the dependence of the dielectric permittivity upon the distance
(ε(r)), developed by Hingerty et al. [10] in the explicit form:
2
2
( ) 78 77( ) ,
( 1)
rp
p rp
e
r r
e
ε = −
−
(3)
where rp = r/2.5. Below, AAPF with the use of expression (3) will be called AAPFh.
2.2. Quantum chemistry approach. In the quantum-chemical calculations, the B3LYP/6-
311+G(d,p) method with a supermolecular approach is used. Calculations are made within the
Gaussian software [11]. The interaction energy is considered as a difference between the energy
of the molecular complex XY and the energies of its components X and Y:
( ) ( ) ( ).XY XY X YE E XY E X E YΔ = − − (4)
The basis sets of the molecular complex XY (dimer-centered basis set) and of the isolated
molecules X and Y (monomer-centered basis sets) are shown in parentheses. The counterpoise
correction (CP) is made to avoid the basis set superposition error, as following:
( ) ( ) ( ).CP
XY XY X YE E XY E XY E XYΔ = − − (5)
In the framework of this approach, the deformation energies for hydrogen peroxide and water
molecules are calculated. It is assumed that nucleic bases are the rigid structures. The deformation
energy is calculated to involve the possible differences between the isolated states of the mole-
cules and of those within complexes:
def complex isolatedE E E= − (6)
85ISSN 1025-6415. Допов. Нац. акад. наук Укр. 2019. № 6
On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules...
Thus, the complete interaction energy in a complex is presented by the formula
complete def .CPE E E= Δ + (7)
In addition, in the framework of the present method, to get an electrostatically neutral struc-
ture, the atoms C1′ that form glycosidic bonds of the nucleic base with the DNA backbone are
changed to H atoms for adenine and thymine and to CH3 group for guanine and cytosine.
3. Calculation results. The interaction of nucleic bases with water molecules has been con-
sidered in the set of works [12, 13], but the interaction with hydrogen peroxide molecules has not
been studied sufficiently yet. Up to now, only the work [14] is known. In the present work, the
stable complexes of hydrogen peroxide molecules with nucleic bases A, T, G, and C are found
and compared to the same complexes with the water molecule.
It is clear that hydrogen peroxide, as well as water, can form hydrogen bonds with nucleic
bases. As known [15], for the recognition of specific DNA sites by an enzyme, it is necessary to
interact through at least two hydrogen bonds. Moreover, due to the structures of a hydrogen per-
oxide molecule and a nucleic base, it is much more favorable for peroxide to form two hydrogen
bonds with base atomic groups, where two different oxygen atoms of the H2O2 molecule are in-
volved in the formation of hydrogen bonds. Unlike a complex with one hydrogen bond, in a com-
plex with two hydrogen bonds, the peroxide molecule should be more stable. It has no possibility
to rotate around hydrogen bonds. Therefore, in accordance with all the mentioned facts, we con-
sider only the complexes with two hydrogen bonds, not taking complexes with one hydrogen
bond into account. It also should be mentioned that the tautomeric forms of nucleic bases have
not been considered in the present work.
For each nucleic base, a few binding sites for the interaction with hydrogen peroxide exist.
These binding sites are schematically shown in Fig. 1. For each site, the length of the hydrogen
bond and the energy minima are calculated. Binding sites from the backbone side are not consid-
ered.
The results of our calculations are presented in Fig. 2 and Table. One can see that, for the
adenine base at sites A-I and A-II, a hydrogen peroxide molecule interacts with this nucleic base
stronger than water molecule (see Table). For sites A-I and A-II, interaction energies are close to
the values obtained in work [14]. The AAPFh method shows that, at site A-III, there is a weak
Fig. 1. The scheme of the sites of adenine (a), thymine (b), guanine (c) and cytosine (d), where the solvent mo-
lecule (H2O or H2O2) can form a complex with a corresponding nucleic base with two hydrogen bonds. Ro man
numerals denote the number of the site
86 ISSN 1025-6415. Dopov. Nac. akad. nauk Ukr. 2019. № 6
O.O. Zdorevskyi, D.V. Piatnytskyi, S. N. Volkov
Interaction energies of complexes of adenine, thymine, guanine, and cytosine with solvent
molecules (H2O or H2O2), as well as the differences between these energies (ΔE = |EH2O2
|–|EH2O|)
calculated by AAPFh and B3LYP methods. Energies are given in kcal/mol. “—” means
that there is no minimum with two hydrogen bonds in this site
Nucleic
bases
H2O2 H2O ΔE
AAPFh (B3LYP) AAPFh (B3LYP) AAPFh (B3LYP)
Adenine I 10.71 (–10.81) –7.95 (–9.65) 2.76 (1.16)
II –9.22 (–11.19) –5.65 (–9.00) 3.57 (2.19)
III –6.76 (—) — (—) — (—)
Thymine I –9.26 (–10.39) –5.54 (–8.64) 3.72 (1.75)
II –8.63 (–11.17) –5.26 (–9.29) 3.37 (1.88)
Guanine I –9.67 (–10.98) –9.06 (–8.45) 0.61 (2.53)
II –9.56 (–13.43) –5.99 (–11.62) 3.57 (1.81)
III –10.36 (—) –6.35 (—) 4.01 (—)
IV –9.02 (–9.83) — (–7.83) — (2.00)
Cytosine I –11.22 (–12.92) –6.82 (–11.11) 4.40 (1.81)
II — (–10.39) –7.40 (—) — (—)
III –7.62 (—) — (—) — (—)
Fig. 2. Complexes of nucleic bases with hydrogen peroxide molecules:
a — adenine; b — thymine; c — guanine; d — cytosine. Numbers are given for
the corresponding hydrogen bond distances between heavy atoms. Upper
number corresponds to the value obtained in AAPFh method, and bottom
number is obtained from B3LYP approach. Distances are given in Å
87ISSN 1025-6415. Допов. Нац. акад. наук Укр. 2019. № 6
On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules...
binding of the H2O2 molecule with bent hydrogen bonds. At the same time, B3LYP method
shows no binding at this site. It should also be mentioned that, in the case of B3LYP method,
water and hydrogen peroxide molecules change their shape insignificantly — deformation ener-
gies do not exceed 0.5 kcal/mol.
Our calculations show that, in the case of thymine, there are two binding sites T-I and T-II
(see Fig. 1, b). The corresponding complexes with a hydrogen peroxide molecule are shown in
Fig. 2, b. For water molecules and hydrogen peroxide, the binding takes place at the same sites of
thymine, but with a significant difference in the interaction energy (see Table). Both our ap-
proaches (AAPFh and B3LYP) give dominance in the interaction energy to a complex with pe-
roxide as compared with the same complex with a water molecule. In the case of B3LYP method, the
deformation energy of peroxide and water molecules plays an insignificant role (< 0.3 kcal/mol).
Complexes with the binding of hydrogen peroxide molecules to guanine (G-I, G-II, G-III,
G-IV) are also shown in Fig. 1, c. Differences in the interaction energies are given in Table. Stu-
dying these complexes by B3LYP method shows that, in position I, a hydrogen peroxide molecu-
le is significantly deformed (2.5 kcal/mol), what is the reason for the differences between hydro-
gen bond distances in AAPFh and B3LYP methods (see Fig. 2, c).
Cytosine has two binding sites (see Fig. 2, d). At site C-I, there is the binding of both of
the water and hydrogen peroxide molecules. In addition, hydrogen peroxide is more energeti-
cally favorable to bind (see Table). At site C-III, there is the binding only of hydrogen peroxide.
For site C-II, there is no binding of hydrogen peroxide in the framework of AAPFh method due
to the geometric features of an H2O2 molecule, which is rigid. As it can be seen from the structure
of the complex, for B3LYP method in position II, hydrogen peroxide dramatically changes its di-
hedral angle (deformation energy is 4.2 kcal/mol) to form two hydrogen bonds with cytosine.
This allows an H2O2 molecule to make a stable complex with cytosine at this cite.
Summarizing the results of our calculations by both methods used in the present work, it
can be seen that, for adenine, thymine, guanine, and cytosine nucleic bases, there are places
which are more favorable for the binding by a hydrogen peroxide molecule rather than by a
water molecule.
4. Conclusions. In the present work, we have obtained the stable configurations of hydrogen
peroxide with DNA specific recognition sites by two methods: the method of atom-atom poten-
tial functions and density functional theory. Both methods show similar results. It can be seen
(see Fig. 2) that it is most probable for hydrogen peroxide to bind to thymine from the side of
atomic groups responsible for the formation of complementary hydrogen bonds. To adenine and
guanine — from the side of major and minor grooves, as well as complementary hydrogen bonds.
To cytosine — from the side of the major groove and the complementary hydrogen bonds.
It should be noted that the protein recognition of a DNA macromolecule can take place as
from the major and minor grooves, depending on the type of an enzyme and on the form of a
double helix. Therefore, the formation of a complex of a nucleic acid with a hydrogen peroxide
molecule, which binds to the bases from the major (see Fig. 1, A-I, C-III, G-I) or minor groove
(see Fig. 1, A-III, G-IV), can prevent the recognition of this base by the enzyme and to block
the DNA replication. On the final stage of the DNA replication, when the double-stranded DNA
is already unzipped up to two single strands, the formation of the complexes of H2O2 molecules
with nucleic bases from the side of complementary hydrogen bonds (TI, T-II, A-II, CI, C-II, G-II,
88 ISSN 1025-6415. Dopov. Nac. akad. nauk Ukr. 2019. № 6
O.O. Zdorevskyi, D.V. Piatnytskyi, S. N. Volkov
G-III) can take place. It should lead to the mistakes in the copying of the genetic infor mation dur-
ing the synthesis of complementary strands.
To sum up, there are definite sites of nucleic bases, where the binding by hydrogen peroxide is
much more advantageous than that by a water molecule. As can be seen from our calculations (see
Table), the energy of the blocking of nucleic bases by a hydrogen peroxide molecule at these sites
is comparable to the energy of the formation of complementary pairs [6]. Consequently, the for-
mation of such complexes is sufficiently probable in cells during the ion beam treatment. In this
way, the processes of genetic information transfer should be blocked in cancer cells.
The present work was partially supported by the National Academy of Sciences of Ukraine
[projects 0118U000662 and 0116U003192].
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Received 04.04.2019
О.О. Здоревський, Д.В. П’ятницький, С.Н. Волков
Інститут теоретичної фізики ім. М.М. Боголюбова НАН України, Київ
E-mail: snvolkov@bitp.kiev.ua
ПРО МОЖЛИВІСТЬ БЛОКУВАННЯ ЦЕНТРІВ СПЕЦИФІЧНОГО ВПІЗНАВАННЯ
ДНК МОЛЕКУЛАМИ ПЕРОКСИДУ ВОДНЮ ПІД ЧАС ІОННОЇ ТЕРАПІЇ
Іонна терапія є одним з найефективніших методів лікування ракових захворювань. Але до цього часу ме-
ханізм дії важких іонів на ракові клітини не визначений. Вивчення процесів фрагментації води під час
іонної терапії показує, що серед великої кількості різних фрагментів у середовищі клітини утворюється
значна концентрація молекул пероксиду водню (H2O2). У роботі наведено результати дослідження конку-
рентної взаємодії молекул Н2О2 та Н2О із центрами специфічного розпізнавання ДНК. Енергії взаємодії
комплексів, що складаються з нуклеїнових основ (аденін, тимін, гуанін і цитозин) разом з молекулами
пероксиду водню і води, обчислені із застосуванням методу атом-атомних потенціальних функцій і теорії
функціонала густини. Знайдено атомні групи нуклеїнових основ, які є більш енергетично вигідними для
зв’язування з молекулами пероксиду водню, ніж з молекулами води. Утворення таких комплексів може
блокувати процес реплікації ДНК на різних етапах і може бути одним з механізмів дії високоенергетичних
іонів на ракові клітини.
Ключові слова: нуклеїнові основи ДНК, пероксид водню, ракова терапія.
А.А. Здоревский, Д.В. Пятницкий, С.Н. Волков
Институт теоретической физики им. Н.Н. Боголюбова НАН Украины, Киев
E-mail: snvolkov@bitp.kiev.ua
О ВОЗМОЖНОСТИ БЛОКИРОВАНИЯ ЦЕНТРОВ СПЕЦИФИЧЕСКОГО УЗНАВАНИЯ
ДНК МОЛЕКУЛАМИ ПЕРОКСИДА ВОДОРОДА В ХОДЕ ИОННОЙ ТЕРАПИИ
Ионная терапия является одним из наиболее эффективных методов лечения раковых заболеваний. Но до
настоящего времени механизм действия тяжелых ионов на раковые клетки не установлен. Изучение про-
цессов фрагментации воды при ионной терапии показывает, что среди большого количества различных
фрагментов в клеточной среде образуется значительная концентрация молекул пероксида водорода
(H2O2). В работе приведены результаты изучения конкурентного взаимодействия молекул H2O2 и H2O с
центрами специфического узнавания ДНК. Энергии взаимодействия комплексов, состоящих из нуклеи-
новых оснований (аденин, тимин, гуанин и цитозин) вместе с молекулами пероксида водорода и воды,
рассчитаны с использованием метода атом-атомных потенциальных функций и теории функционала
плотности. Найдены атомные группы нуклеиновых оснований, с которыми молекула пероксида водорода
связывается значительно энергетически выгоднее, чем молекула воды. Образование таких комплексов мо-
жет блокировать процесс репликации ДНК на разных стадиях и может быть одним из механизмов воз-
действия высокоэнергетических ионов на раковые клетки.
Ключевые слова: нуклеиновые основания ДНК, пероксид водорода, терапия рака.
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