Dt. Goodhead et al., EFFECTS OF RADIATIONS OF DIFFERENT QUALITIES ON CELLS - MOLECULAR MECHANISMS OF DAMAGE AND REPAIR, International journal of radiation biology, 63(5), 1993, pp. 543-556
Citations number
94
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging","Nuclear Sciences & Tecnology
Studies of ionizing radiations of different quality are discussed with
particular emphasis on damage to DNA of mammalian cells. Three relate
d themes are followed. Firstly, inactivation and mutation experiments
with ultrasoft X-rays and slow heavy ions, coupled with theoretical an
alyses of the structures of the radiation tracks, have emphasized the
biological importance of localized track features over nanometre dimen
sions. This led to the suggestion that the critical physical features
of the tracks are the stochastic clusterings of ionizations, directly
in or very near to DNA, resulting in clustered initial molecular damag
e including various combinations of breaks, base damages, cross-links,
etc. in the DNA. The quantitative hypotheses imply that final cellula
r effects from high-LET radiations are dominated by their more severe,
and therefore less repairable, clustered damage, and that these are q
ualitatively different from the dominant low-LET damage. Second, relat
ive effectiveness of different types of radiation led to questions on
the mechanisms of induction of chromosome exchanges. The high efficien
cy of ultrasoft X-rays, despite their very short track lengths, sugges
ted that single sites of DNA damage may lead to exchanges by a molecul
ar process involving interaction with undamaged DNA. Also it is shown
that a single site-specific DNA break, introduced by restriction enzym
es, sometimes leads to a large deletion when misrepaired by cell extra
cts. These deletions occur between short DNA repeats, and are therefor
e a form of 'illegitimate' recombination, but clearly do not involve t
he interaction of two damage sites. Third, it was shown that cells fro
m patients with the radiosensitive disorder ataxia-telangiectasia (AT)
lack a post-irradiation recovery process. The sensitivity of AT cells
to high LET radiations was found to be reduced relative to that for n
ormal cells, reinforcing the concept that high LET damage is less easy
to repair. AT patients are prone to lymphoreticular cancers, and thei
r cells show characteristic chromosomal rearrangements, which may be a
ssociated with misrepair at specific genomic sequences. Similarly, stu
dies of radiation-induced leukaemia in the mouse have implicated rearr
angement at specific interstitial chromosome sites, which are rich in
telomere-like repeat sequences.