170 unifying physics of accelerators, lasers and plasma
then form hydrogen peroxide and cause single-strand DNA
breaks.
We should also note that the effects described above are
also very similar to the case of irradiation by protons, taking into account that, in this instance, the electrons and
bremsstrahlung photons are produced when the protons lose
their energy to electrons of the absorbing medium.
Several minor DNA defects — such as one-strand dimer
formations (caused by UV light — see bottom part of Fig. 9.3)
or single-strand breaks could be corrected by the internal cell
mechanism, base excision repair, which involves endonucleases and DNA polymerase. Nevertheless, some errors can also
appear at this step (for example, wrong nucleotide(s) inserDouble-strand breaks repre- tion could cause a future coding mismatch).
sent the most detrimental
Double-strand breaks are more difficult to repair and thus
damage produced in DNA by represent the most detrimental damage produced in DNA by
ionizing radiation.
ionizing radiation. When a cluster of complex DNA damage
events occur together, for example from dense ionization at
the terminal end of an energetic electron track, there is the
highest probability of either mis-repair or failure to repair
damage. A loss of entire parts of the chromosomes containing tumor-suppressor genes — an amplification of oncogenicpotential regions — could lead to carcinogenesis, the creation
of tumor cells. Unrepairable damage can trigger the apoptosis
mechanism, where defective cells undergo “cell suicide” and
are, thus, eliminated. Mis-repair of DNA with cross-linked
or mutated chromosomes may not be immediately lethal, but
will lead to further DNA damage or cell death when the cell
next attempts division — mitotic catastrophe.
Various examples of the consequences of DNA irradiation
are shown on the right side of Fig. 9.3. They include temporary arrest at different stages of the cell cycle (mitosis (M),
both check-points (G1 and G2), or DNA replication/synthesis
(S)). The irradiation effects also may include inhibition of
transcription and a variety of cell division abnormalities, all
of which could result in a defective cell death.
In molecular biology, a small
The positive effects of ionizing radiation are caused by the
molecule drug (or a small same mechanisms, since what could be detrimental for a norcompound) is a low molecu- mal cell could also be destructive for a malignant one.
lar weight organic compound
In order to further enhance the destructive effect of X-rays
that may help to regulate bi- on malignant cells, some concomitant agents such as small
ological processes.
molecule oncology drugs could be involved. The upper limit
for a small molecule’s weight is approximately 900 daltons,
which allows rapid diffusion across cell membranes so that
Dalton (Da) is the standard they can reach intracellular sites of action.
unit defined as one twelfth of
The effects of irradiation and the use of concomitant
the mass of an unbound neu agents can lead to an increased number of difficult-to-repair
tral atom of C 12 in its nuinter-strand cross links,
clear
as shown in Fig. 9.3. The apoptosis
and electronic ground
state. In other words, one Da mechanism, launched by the strong synergetic effect of these
is approximately equal to a two techniques, leads to a more efficient elimination of mamass of a proton or neutron. lignant cells.
then form hydrogen peroxide and cause single-strand DNA
breaks.
We should also note that the effects described above are
also very similar to the case of irradiation by protons, taking into account that, in this instance, the electrons and
bremsstrahlung photons are produced when the protons lose
their energy to electrons of the absorbing medium.
Several minor DNA defects — such as one-strand dimer
formations (caused by UV light — see bottom part of Fig. 9.3)
or single-strand breaks could be corrected by the internal cell
mechanism, base excision repair, which involves endonucleases and DNA polymerase. Nevertheless, some errors can also
appear at this step (for example, wrong nucleotide(s) inserDouble-strand breaks repre- tion could cause a future coding mismatch).
sent the most detrimental
Double-strand breaks are more difficult to repair and thus
damage produced in DNA by represent the most detrimental damage produced in DNA by
ionizing radiation.
ionizing radiation. When a cluster of complex DNA damage
events occur together, for example from dense ionization at
the terminal end of an energetic electron track, there is the
highest probability of either mis-repair or failure to repair
damage. A loss of entire parts of the chromosomes containing tumor-suppressor genes — an amplification of oncogenicpotential regions — could lead to carcinogenesis, the creation
of tumor cells. Unrepairable damage can trigger the apoptosis
mechanism, where defective cells undergo “cell suicide” and
are, thus, eliminated. Mis-repair of DNA with cross-linked
or mutated chromosomes may not be immediately lethal, but
will lead to further DNA damage or cell death when the cell
next attempts division — mitotic catastrophe.
Various examples of the consequences of DNA irradiation
are shown on the right side of Fig. 9.3. They include temporary arrest at different stages of the cell cycle (mitosis (M),
both check-points (G1 and G2), or DNA replication/synthesis
(S)). The irradiation effects also may include inhibition of
transcription and a variety of cell division abnormalities, all
of which could result in a defective cell death.
In molecular biology, a small
The positive effects of ionizing radiation are caused by the
molecule drug (or a small same mechanisms, since what could be detrimental for a norcompound) is a low molecu- mal cell could also be destructive for a malignant one.
lar weight organic compound
In order to further enhance the destructive effect of X-rays
that may help to regulate bi- on malignant cells, some concomitant agents such as small
ological processes.
molecule oncology drugs could be involved. The upper limit
for a small molecule’s weight is approximately 900 daltons,
which allows rapid diffusion across cell membranes so that
Dalton (Da) is the standard they can reach intracellular sites of action.
unit defined as one twelfth of
The effects of irradiation and the use of concomitant
the mass of an unbound neu agents can lead to an increased number of difficult-to-repair
tral atom of C 12 in its nuinter-strand cross links,
clear
as shown in Fig. 9.3. The apoptosis
and electronic ground
state. In other words, one Da mechanism, launched by the strong synergetic effect of these
is approximately equal to a two techniques, leads to a more efficient elimination of mamass of a proton or neutron. lignant cells.