160
N. ARLEY
Another fundamental problem in radiobiology is the problem of what
are the mechanisms of the effects of radio-protecting, as well as radiosensitizing, substances. It is well known that accumulated evidence on
chemical protection does not now permit an unequivocal recognition of
the underlying mechanisms (p. 51-52 in [11]). However, two mechanisms
seem at the present time to be generally thought of as being the most important ones, on the one hand the scavenging effect of the protector molecules, P,
on the intermediary free radicals, X, formed in the solvent by the irradiation, on the other hand the masking effect in which the protector molecules,
P, attach themselves to the solute molecules, E, under investigation in such
a way as to mask their sensitive sites against the inactivating attack of the
free radicals, X, leading to the biological damage in question.
Both these problems are solved in the model and the recipe for the
determination of the numerical values of the parameters of the model proposed in the paper reported here for the special case of enzyme inactivation
in solution by ionizing radiation. For the details I beg to refer you to the
original papers quoted. Here I shall finish by just indicating the proposed
recipe for extracting the information we are looking for as discussed above
from the pertinent experimental data-again stressing that these experimental data seem not yet to have been obtained, but that we hope soon to
be able to obtain them in my Oslo institute.
I assume as a first approximation, which I have generalized in a second
paper not yet published, that the enzyme E is predominantly inactivated by
one free radical X formed in the water by the irradiation. Under this
assumption the model contains in all 5 parameters denoting 5 kinetic rate
constants of 5 chemical reactions. These 5 rate constants may be deduced
from experimental data as follows. For each irradiation dose D one has to
calculate the time
te=iXD(1
(1)
where te is the time of observation assumed here to coincide with the time
at the end of the irradiation, started at t = 0; I is the number of radicals
formed per unit time and iX is a proportionality constant converting dose D
to total number of radicals formed
lte =iXD
(2)
(The mathematical formalism of the model also covers the case where
there is a time lag between the time of observation and the time at the end
of the irradiation, but this case does not seem to occur in any experiments
so far and it seems to be inappropriate to make the experiments in such a
way.) One then has to plot
In (E (Eo) versus i;
(3)
N. ARLEY
Another fundamental problem in radiobiology is the problem of what
are the mechanisms of the effects of radio-protecting, as well as radiosensitizing, substances. It is well known that accumulated evidence on
chemical protection does not now permit an unequivocal recognition of
the underlying mechanisms (p. 51-52 in [11]). However, two mechanisms
seem at the present time to be generally thought of as being the most important ones, on the one hand the scavenging effect of the protector molecules, P,
on the intermediary free radicals, X, formed in the solvent by the irradiation, on the other hand the masking effect in which the protector molecules,
P, attach themselves to the solute molecules, E, under investigation in such
a way as to mask their sensitive sites against the inactivating attack of the
free radicals, X, leading to the biological damage in question.
Both these problems are solved in the model and the recipe for the
determination of the numerical values of the parameters of the model proposed in the paper reported here for the special case of enzyme inactivation
in solution by ionizing radiation. For the details I beg to refer you to the
original papers quoted. Here I shall finish by just indicating the proposed
recipe for extracting the information we are looking for as discussed above
from the pertinent experimental data-again stressing that these experimental data seem not yet to have been obtained, but that we hope soon to
be able to obtain them in my Oslo institute.
I assume as a first approximation, which I have generalized in a second
paper not yet published, that the enzyme E is predominantly inactivated by
one free radical X formed in the water by the irradiation. Under this
assumption the model contains in all 5 parameters denoting 5 kinetic rate
constants of 5 chemical reactions. These 5 rate constants may be deduced
from experimental data as follows. For each irradiation dose D one has to
calculate the time
te=iXD(1
(1)
where te is the time of observation assumed here to coincide with the time
at the end of the irradiation, started at t = 0; I is the number of radicals
formed per unit time and iX is a proportionality constant converting dose D
to total number of radicals formed
lte =iXD
(2)
(The mathematical formalism of the model also covers the case where
there is a time lag between the time of observation and the time at the end
of the irradiation, but this case does not seem to occur in any experiments
so far and it seems to be inappropriate to make the experiments in such a
way.) One then has to plot
In (E (Eo) versus i;
(3)