Simulation of the effect of N2O on DNA damage by ionizing radiation

JIŘÍ BARILLA, PAVEL SIMR, KVĚTUŠE SÝKOROVÁ

Faculty of Science

J. E. Purkinje University in Usti nad Labem

Pasteurova 3544/1, 400 96 Usti nad Labem

CZECH REPUBLIC

form aggressive OH radicals. A mathematical simulation model developed using hybrid Petri nets is

used to analyze this dynamic process. Hybrid Petri nets allow us to quickly create a mathematical

simulation model and explore the system under study to obtain detailed information for practical

applications.

Key-Words: Hybrid Petri nets, SSB formation, ionizing radiation, radical clusters, N2O

Received: February 19, 2023. Revised: February 19, 2024. Accepted: May 16, 2024. Published: July 2, 2024.

effect is unlikely for low-LET radiation and is

neglected in our mathematical simulation model.

Much more relevant to us is the damage to the

DNA molecule by an indirect effect, where the

energy transfer occurs at some distance from the

DNA molecule. In our mathematical simulation

model, we assume that the damage to the DNA

molecule occurs through indirect effects.

a radical cluster is formed when the energy of

the radical cluster, chemical reactions of the

chemicals in the cluster occur with simultaneous

diffusion of these compounds into the

surroundings. If a DNA molecule is close to the

reactions and their diffusion into the

surroundings.

radiation so that N2O molecules react with the

hydrated electrons to form aggressive OH

suitable tool to simulate the dynamic process of

DNA molecule damage by aggressive radicals in

the presence of N2O during irradiation with

ionizing radiation. These Petri nets allow the

rapid generation of a mathematical simulation

model using a graphical tool and quick analysis

under different input conditions.

mathematical simulation models of the chemical

stage of the radiobiological mechanism. Initially, we

contains a minimal number of free parameters, which

provides greater model plausibility. The initial model

parameters are mostly taken from the literature

[10][12][13][14][18][19][21][22][23][24][25][31]

[32] and from our previous analyses based on

experimental data.

radical cluster, which initially contains primary

products (

chemical stage of the radiobiological

mechanism, which includes both the dynamics

of the chemical reactions according to Table 1,

including the diffusion of chemicals into the

surroundings of the radical cluster and the

Figure 1. Simulation model of SSB formation represented by hybrid Petri nets.

connected by arrows. The circles indicate the

places that represent the chemical amounts, the

size of the volume in which the chemical is

found, and the constants used in the

mathematical model. The rectangles represent

the transitions that cause a change in the value of

VH2, VH2O2, VOHM, and VHO2 correspond

to the volumes VH, , , ,, ,

, 

indicates the chemical. The corresponding

transitions that cause a volume change at the

corresponding location are then named TVH,

TVOH, TVe, TVH3O, TVOHM, TVH2,



species , , , , , , , 

, O2 and DNA (number of phosphate bonds)

respectively, which are placed in corresponding

, , , , , , ,



constants of the chemical reactions from Table 1.

the initial yield of primary radiolysis products,

the size of the resulting cluster, and so on. The

input parameters of the mathematical simulation

model were set based on the analysis of

[11]. These analyses were carried out in our

of water G0 under anoxic conditions

[14][18][19][20][23].

transition energy of 300 eV, the following initial

chemical numbers were determined

chemicals according to the reactions shown in

Table 1, where the reaction constants of these

species diffuse into the surroundings. In our

work, we assume spherical symmetry for the

time evolution of the radical cluster, which

corresponds to low-LET radiation. The diffusion

coefficients are then listed in Table 2 and taken

from the literature. The time evolution of the

radical cluster for the chemicals in Table 2

follows transition functions 1-9.

aggressive radicals results in the formation of