no information about such effects on humans in available that is suitable for setting radiation limits, it is essential that the possibility of effects on the central nervous system be adequately assessed. Because the ideal of obtaining data from primates exposed to heavy ions is unlikely to be realized, critical animal experiments must be carefully crafted and executed.
This section touches on new techniques being used for the qualitative assessment of mutations and chromosomal aberrations, and the characterization of molecular events involved in tumor development. It is assumed that significant progress in the next few years will be made in the above broad areas.
As pointed out in previous chapters, estimates of cancer risk posed by low-LET radiation are quite well founded and are based on fairly extensive animal but limited human studies (those of atomic bomb survivors). Testing the reliability of the extrapolation of results from rodent studies to humans would require a better understanding of the mechanism of formation of specific tumor types, both background and x ray induced, for both human and animal models (with the same tumor type). Although rather little information is available on the genetic alterations associated with radiation-induced tumors, the methods exist and candidate genes such as p53 have been proposed. 2 What remains to be developed are sufficiently sensitive assays for detecting mutations in nonselectable genes that could be markers of early stages in tumor development. While specific polymerase chain reaction (PCR) methods are becoming more sensitive, they are still 1 or 2 orders of magnitude away from being able to detect induced mutations at the needed frequencies of occurrence, typically at mutation frequencies of 1 in 107 cells.
Limited data are available on cancer induction in rodents exposed to high-LET radiation; information on other biological effects is also sparse. It will be necessary to conduct additional cancer studies in rodents exposed to different types of high-LET radiation and to characterize the resulting tumors at the molecular level. In fact, for high-LET radiation, the conversion of DNA lesions into mutations is not well understood. In order to better simulate conditions of exposure during spaceflight, it is necessary to consider the effectiveness of induction of mutations by low-dose-rate exposure to both high-and low-LET radiation. The use of fluorescence in situ hybridization allows reciprocal translocations to be assessed following protracted exposure. A translocation is a significant chromosomal end point when considering genomic alterations that are associated with adverse health effects. Assays are also under development for detecting low-frequency aberrations in genes above background. Although currently available only for selectable genes such as that for HPRT (hypoxanthine phosphoribosyl transferase), for which mutants have a growth advantage (i.e, they are selected for their ability to grow faster than non-mutants), it is anticipated that new assays will be available for nonselectable tumor genes and genes such as p53 and other tumor suppressor genes in the future.
The identification of populations that are genetically susceptible to cancer development is also of considerable importance. Uncovering the mechanisms involved in tumor formation is critical for this purpose but despite considerable progress is still a distant goal. A more attainable goal may be development of surrogate assays for predicting increased sensitivity for tumor induction. The G2 chromosomal aberration assay described by Jones et al.3 is promising. It appears to be able to identify individuals who have at least increased radiosensitivity of lymphocytes, and in one case, this increase was quite marked in about 40% of breast cancer patients.4 More work and probably a number of modifications to the technique are in order before it can be used as a predictor of radiation sensitivity.
The influence of microgravity on the effects of low-LET radiation have been reviewed by Horneck and by Nelson.5,6 Most experiments showed negligible or small effects of microgravity on radiation-induced changes. Typical changes observed had to do with increased chromosomal alterations in fruit flies and in Tradescantia (the spiderwort plant) following irradiation before lift-off. Horneck suggests that changes in chromosomal structure or position in microgravity could have prevented effective rejoining of chromosomes. On the other hand, there was no control in such experiments for vibration or acceleration during lift-off or return of the satellites. In another example cited in these reviews, an experiment measuring viability in yeast,