Critiques of NCRP Report No. 136 re: 1) non-threshold model for
action of ionizing radiation in the very low dose range, 2) the assumption that
radiation-induced DNA double strand breaks (dsbs) are different from spontaneous dsbs and
peculiarly difficult substrates for the cell to cope with, 3) biased presentations of data
on atomic bomb survivors and 4) omission from the Report of relevant reports for threshold
effects in radiation tumorigenesis after irradiation at extremely low dose-rates.
Sohei Kondo, 6-2-13 Habikigaoka, Habikino City 583-0864 Japan;
E-mail: skondo@taurus.bekkoame.ne.jp
1) Non-threshold model for action of ionizing radiation in the
very low dose range
The Report states that even at the smallest doses, some of the target
cells receive relatively large amounts of radiation energy when they are struck by a
single particle. This is a biased statement because live cells are actually exposed to
various chemicals in nature and endogenous toxin. Therefore, the question is whether the
dose of about 1 mGy given to a cell struck by a single particle is larger than the
chemical dose given to that cell by spontaneous toxin. This question is equivalent to the
question whether DNA damage induced in a cell by 1 mGy of low LET radiation is more severe
than DNA damage induced spontaneously. This is the subject of discussion in the following
paragraph.
2) The assumption that radiation-induced DNA double strand breaks
(dsbs) are different from spontaneous ones and peculiarly difficult substrates for the
cell to cope with.
This is the basic assumption adopted in NCRP Report No. 136. It is
mentioned in the Report that DNA damage other than dsbs is produced in cells by
spontaneous factors more abundantly than by radiation but the damage is almost completely
repaired. The Report emphasizes that dsbs occurring in unirradiated cells are sealed
enzymatically as part of normal processes but dsbs induced by ionizing radiation have
unusual end groups and hence peculiarly difficult substrates for the cell to cope with and
thought by most radiobiologists to be the lesions that endow ionizing radiation with its
uniquely toxic effects (Ward, 1995).
Recently, studies of Nijmegen Breakage Syndrome (NBS), a very rare
autosomal recessive genetic disorder, have revealed that NBS results from a gene mutation
on chromosome 8q21, cells from NBS patients are two-fold sensitive to killing by X rays
than wild-type cells due defect in the repair of dsbs, in 40% of the NBS patients,
lymphoma, leukemia and other tumors were noted before age of 21 years and congenital
malformations were noted in about 50% of the patients (The international Nijmegen breakage
syndrome study group, Arch Dis Child, 82, 400-406, 2000). Therefore, the defect in repair
of DNA dsbs in the NBS patients is responsible for high incidence of malignancy and
malformations. In other words, spontaneous DNA dsbs are highly toxic if they are not
normally repaired. These results are not compatible with the NCRP Report ‘s basic
assumption that radiation-induced DNA dsbs are uniquely toxic damage.
The number of dsbs produced spontaneously in human cells in a growing
phase is estimated to be about 10 per cell per day. Since 1 mGy of gamma rays induces 0.04
dsb per cell, the risk of 1 mGy gamma rays per day is only 0.4% of the spontaneous DNA dsb
damage. Of course, radiation-induced dsbs may not be perfectly identical with spontaneous
dsbs in regard to the detailed molecular structure. Even if this is the case, we may
assume that exposure to ionizing radiation at the level of 1 mGy per day is no more
hazardous than spontaneous risk without radiation. Supporting evidence for this conjecture
from an epidemiologic study will be discussed in paragraph 4. |
