  Although DNA damage is widely viewed as a critical target for the induction
of cell killing by ionizing radiation, the exact nature of DNA damage
responsible for these effects is unknown. To address this issue, the
probability of forming lethal damage by single proton tracks, derived from
published survival data for Chinese hamster V79 cells irradiated by protons
with energies from 0.57 to 5.01 MeV, has been compared to estimated yields of
clustered DNA lesions and repair outcomes calculated with Monte Carlo models.
The reported studies provide new information about the potential relationship
between the induction and repair of clustered DNA damage and trends in the
expected number of lethal events for protons with increasing linear energy
transfer (LET). A good correlation was found between the number of lethal
events in V79 cells and the induction of double-strand breaks (DSBs) consisting
of 3 or more elementary DNA lesions. For the yields of other types of DNA
damage, as well as point mutations formed through the misrepair of base damage
and single-strand breaks, observed trends with increasing LET are not
consistent with trends in the yields of lethal events. This observation
suggests that the relative biological effectiveness (RBE) of protons of varying
quality may be more closely related to the induction of complex DSBs rather
than other forms of damage.
