Question 1: What are the carcinogenic risks following irradiation by protons and HZE particles?
Answering this key question requires that two related research questions be addressed. First, can the risk due to irradiation by protons in the energy range of the space environment be predicted on the basis of the risk posed by exposure to low-LET radiation; i.e., is it appropriate to assume that the quality factor is 1, and is there evidence for repair of damage in cells following fractionated exposure to protons and HZE particles? Second, what are the appropriate quality factors for making risk calculations with respect to HZE particles?
The answers to these questions are fundamental to understanding the risk of contracting cancer as a result of travel in deep space. Without these answers, it will not be possible to improve the understanding of risk beyond the current state. These important questions can be addressed using solely ground-based studies if appropriate funding and additional radiation resources such as accelerator time are made available.
Initial studies of the effects of exposure to protons should focus on cellular effects that are relevant to cancer. Research with cells would provide a more rapid resolution than would tumor induction studies with animals of whether effects of exposure to high-energy protons are similar to those arising from low-LET radiation. Theoretical models of radiation effects as well as currently available data for cellular and tumorigenic effects of exposure to protons (mostly at energies lower than those encountered in space) would argue that risks due to proton irradiation are similar to those from low-LET irradiation. To determine whether such a prediction is appropriate for higher-energy protons, the task group recommends that a series of studies be conducted in several cellular systems, including human fibroblasts and lymphocytes, to examine the effects of protons in the 1-GeV energy range on cell killing, induction of chromosomal aberrations, and induction of gene mutations. To bridge the gap between in vitro and in vivo results, chromosomal aberrations could also be studied in lymphocytes from animals irradiated in vivo. By conducting such studies with both acute and fractionated exposure regimens, it would be possible to determine whether fractionation effects (sparing of radiation response by allowing for DNA repair between fractions) similar to those for low-LET radiation exist. Animal carcinogenesis experiments with protons should be conducted only if the results of cellular studies indicate discrepancies from the predictions. If, on this basis, tumorigenesis studies are warranted, the same animal models recommended for the study of tumorigenesis following exposure to HZE particles (described below) should be employed. Facilities to conduct proton experiments are available at Brookhaven and Los Alamos national laboratories in the United States (see Appendix C). Lower-energy protons such as those at Loma Linda University Medical Center Proton Therapy Facility are somewhat useful for studies related to solar events. Although considerable data are already available for protons in this energy range, these data are not satisfactory to answer questions related to high-energy protons in the 1-GeV energy range. If animal studies are required, irradiation of sufficient numbers of animals would generally require at least 1 to 1.5 years, while conduct of the animal studies subsequent to completion of the irradiation would require 3 to 4 additional years.