months at very low dose rates or with fractionated exposures. The cumulative effect of multiple low doses of less than 10 mGy delivered over extended periods has to be explored further. The development of in vitro transformation assays utilizing nontransformed human diploid cells is judged to be of special importance.
Research Need 4: Identification of molecular mechanisms for postulated hormetic effects at low doses
Definitive experiments that identify molecular mechanisms are necessary to establish whether hormetic effects exist for radiation-induced carcinogenesis.
Research Need 5: Tumorigenic mechanisms
Further cytogenetic and molecular genetic studies are necessary to reduce current uncertainties about the specific role of radiation in multistage radiation tumorigenesis.
Research Need 6: Genetic factors in radiation cancer risk
Further work is needed in humans and mice on gene mutations and functional polymorphisms that influence radiation response and cancer risk.
Research Need 7: Heritable genetic effects of radiation
Further work should be done to establish (1) the potential roles of DNA double-strand break repair processes in the origin of deletions in irradiated stem cell spermatogonia and oocytes (the germ cell stages of importance in risk estimation) in mice and humans and (2) the extent to which large radiation-induced deletions in mice are associated with multisystem development defects. In humans, the problem can be explored using genomic databases and knowledge of mechanisms of origin of radiation-induced deletions to predict regions that may be particularly prone to radiation-inducible deletions.
With respect to epidemiology, studies on the genetic effects of radiotherapy for childhood cancer should be encouraged, especially when they can be coupled with modern molecular techniques (such as array-based comparative genomic hybridization).
Research Need 8: Future medical radiation studies
Most studies of medical radiation should rely on exposure information collected prospectively, including cohort studies as well as nested case-control studies. Future studies should continue to include individual dose estimation for the site of interest, as well as an evaluation of the uncertainty in dose estimation.
Studies of populations with high- and moderate-dose medical exposures are particularly important for the study of modifiers of radiation risks. Because of the high level of radiation exposure in these populations, they are also ideally suited to study the effects of gene-radiation interactions, which may render particular subsets of the population more sensitive to radiation-induced cancer. Genes of particular interest include BRCA1, BRCA2, ATM, CHEK2, NBS1, XRCC1, and XRCC3.
Of concern for radiological protection is the increasing use of computed tomography (CT) scans and diagnostic X-rays. Epidemiologic studies of the following exposed populations, if feasible, would be particularly useful: (1) followup studies of persons receiving CT scans, especially children; and (2) studies of infants who experience diagnostic exposures related to cardiac catheterization, those who have recurrent exposures to follow their clinical status, and premature babies monitored for pulmonary development with repeated X-rays.
There is a need to organize worldwide consortia that would use similar methods in data collection and follow-up. These consortia should record delivered doses and technical data from all X-ray or isotope-based imaging approaches including CT, positron emission tomography, and single photon emission computed tomography.
Research Need 9: Future occupational radiation studies
Studies of occupational radiation exposures, in particular among nuclear industry workers, including nuclear power plant workers, are well suited for direct assessment of the carcinogenic effects of long-term, low-level radiation exposure in humans. Ideally, studies of occupational radiation should be prospective in nature and rely on individual real-time estimates of radiation doses. Where possible, national registries of radiation exposure of workers should be established and updated as additional radiation exposure is accumulated and as workers change employers. These registries should include at least annual estimates of whole-body radiation dose from external photon exposure. These exposure registries should be linked with mortality registries and, where they exist, national tumor (and other disease) registries. It is also important to continue follow-up of workers exposed to relatively high doses, that is, workers at the Mayak nuclear facility and workers involved in the Chernobyl cleanup.
Research Need 10: Future environmental radiation studies
In general, additional ecological studies of persons exposed to low levels of radiation from environmental sources are not recommended. However, if there are disasters in which a local population is exposed to unusually high levels of radiation, it is important that there be a rapid response not only for the prevention of further exposure but also for scientific evaluation of possible effects of the exposure. The data collected should include basic demographic information on individuals, estimates of acute and possible continuing exposure, the nature of the ionizing radiation, and the means of following these individuals for many years. The possibility of enrolling a comparable nonexposed population should be considered. Studies of persons exposed environmentally as a result of the Chernobyl disaster or as a re-