DESARROLLO DE LA SESION DE APRENDIZAJE:

The main impetus to the reanalysis of published biophysical data by Watt and Coworkers is an earlier theoretical treatment of the hit and target theory (Watt, 1975) which indicated that energy based parameters may not be the most appropriate for the description of radiation effects in biological systems. This contention was later proved experimentally through the inactivation of enzymes in the dry state and in vacuum (Watt et al, 1984 and 1981). The results showed that for fast charged particles, the whole enzyme molecule constituted the target; inactivation followed the single hit in the single target model, where the hit is a single ionisation and the target is the entire biomolecule; the LET appeared as a reasonable indicator of radiation action; the 6-rays could efficiently induce damage. However for slow heavy particles in an energy region where the LET is approximately constant, but where the type of physical interaction changed from mainly ionising to predominantly elastic events, the effect cross-section could differ by an order of magnitude. This demonstrated that the degree of radiation damage was determined predominantly by the frequency of the physical interaction and not necessarily by the amount of energy transfer.

In their subsequent work a reanalysis of published data was made. The objective was to identify the main mechanism responsible for radiation damage and to determine physical parameters that better specify radiation quality. The analysis was made for the inactivation of enzymes, viruses, yeast and mammalian cells with fast ions (Cannell and Watt, 1985) and mammalian cells with photons (Chen and Watt, 1986) over a wide energy range. With appropriate modifications it was extended to the inactivation of metallo-enzymes by characteristic X-rays (Jawad and Watt, 1987) and by incorporated radionuclides (Younis and Watt, 1989).

The philosophy of approach in that analysis, was to avoid energy based parameters and to represent the general trends of radiation effect in a manner which, ideally, would be independent of both the target and radiation type. The degree of radiation damage was therefore expressed in terms of the intrinsic efficiency ej, which represents the total probability that a charged particle track entering the radiosensitive target will induce the biological end point of interest. Thus

e. = Og / Gg 2.2a

Where ce is the effect cross section for induction of the biological effect. In the case of track segment experiments with fast ions it was obtained directly (from values given by respective authors), otherwise the following conversion relation was used:

= 1.6 X 10'®. Lj. .(-)■ L 2.2

Where p, the density, is taken as Igmcm"^; Dq (grays ) is the mean inactivation dose (or D37 in some cases) is taken from the dose-response curve. Lx(kev/pm) is the

track-averaged LET for the pertinent charged particles, in the case of accelerated ions in track segment experiments it refers to the primary ion’s energy. For photon radiations it was for the electrons in the slowing down equilibrium spectram.

The geometrical cross sections, Og are normalising factors representative of the radiosensitive sites for killing of the different cells and biomolecules. For enzymes it is taken as the whole biomolecule; for viruses it is assumed to be the whole system less the projected area of the protein coat; for more organised cells it is unknown. Watt et al (1985) and Watt (1989) took it to be the projected area of intra nuclear DNA. The basis of the selection of Og for eukaryotic cells is discussed in Watt (1989). With biological effectiveness expressed in terms of intrinsic efficiencies, its correlation with various parameters which may be considered for the specification of radiation quality, such as Loo, Lj), Lp and the Ij was made. Some of the results (see also figure 2.1) are the following:

a) Poor correlation was obtained between the conventional radiosensitive parameter 1/Dq

with Lp, or with Lp, or with Ij compared to the correlation between the intrinsic efficiency and the same physical parameters. This, they inferred, suggests that absorbed dose is an

inferior parameter for dosimetric purposes. The parameter linear primary ionisation (Ij) was identified as suitable for the specification of radiation quality.

b). Plot of the intrinsic efficiency against the Ij of radiations changes slope at Ij about 0.55 per nm when double stranded DNA is present in the cells, or in Tl-phage, but not in enzymes, or in <j)X-174 phage with single stranded DNA. This was interpreted as an indication that DNA double strand breaks were the critical lesions for the inactivation of cells containing double-stranded DNA.

c) electrons and photons have intrinsic efficiencies of damage approaching an order of magnitude less than those of heavy ions at equal values of and could also just attain saturation when at their most damaging state with of 0.55 per nm.

d) There was an order of magnitude difference between the intrinsic efficiency for the inactivation of targets containing double stranded DNA compared to those biomolecules containing single stranded nucleic acids. This was interpreted as an indication that a single strand break might lead to the inactivation of the single-stranded objects, but for more organised cells the critical lesions were the DNA double strand breaks whose probability of occurrence depended on the matching of the strand separation with the ionisation mean free path.

The analysis was however restricted to cellular inactivation as the biological endpoint. Because of the important implications of the results for radiation dosimetry, protection and therapy (Watt et al, 1985) it is essential that the validity of the inferences with respect to other cellular effects of radiations be tested. Therefore, in the present work, the analysis of data was extended to mutation induction, chromosome aberrations, strand breakage and transformations. A discourse of the radiobiological significance of the other endpoints, the treatment of the respective data and the results is preceded by a brief description of the calculations of the physical data required for the analyses.

heavy ions 0 2 photons. 10® 1 h

FIGURE 2.1: In (A) The "normalised" effect cross section for cellular loss of reproductive capacity plotted against Ij. The difference in the damage capability of the photons relative to the heavy ions, of the same Ij is clearly evident In 2.1(B) the same cross sections are plotted against the radiation's mean free path ( l/li) . Note the monophasic behaviour of the upper curve which pertains to the inactivation of phages containing single stranded DNA. The figures were adapted from Chen and Watt (1986) and Watt and Kadiri (1990) where the sources of the original data are given.

2.4 CALCULATION OF PHYSICAL DATA.