The Radiosensitivity of Germ Cells

Summary The radiosensitivity of germ cells depends on ( a ) the criterion by which it is assessed, and ( b ) the developmental stage at the time of irradiation. For any given parameter and cell‐type, the final effect exerted by ionizing radiations depends on the genetic make‐up and age of the organism; type of irradiation; method of irradiation (acute, fractionated, chronic at different dose rates); oxygen tension; and temperature. Variations between different developmental stages may be due to inherent changes in oxygenation, metabolic activity, chromosomal configuration; and other factors, as yet to be determined, are probably also involved. The yield of mutations observed after irradiation of different developmental stages may be at least partly determined by the selective elimination, during subsequent development, of cells sensitive to immediate or delayed cell‐death. In general, mitotically active gonia, particularly in mammals, are highly sensitive to cell‐killing. In some species, inhibition of mitosis may play a considerable part in the final expression of radiation damage. Paradoxically, permanent sterilization in male rodents is most readily achieved by irradiating mitotically inactive primordial germ cells before or shortly after birth. In adult males of all species, permanent sterilization only occurs if all the primary gonia are destroyed. The last pre‐meiotic generation of spermatogonia appears to be more sensitive to cell‐death than are earlier generations; the difference is correlated with the relative durations of the G 1 , S and G 2 periods, at least in adult mice. It is possible that mammalian pre‐meiotic oogonia are also more sensitive than preceding generations. Interpretation of observations on insects is complicated by radiation‐damage to nurse cells which may secondarily hamper the development of the germ cells. The incidence of chromosomal aberrations and mutations following gonial irradiation is relatively low, possibly due to selective elimination. A proportion of gonia which survive to give rise to differentiated gametes may carry a variety of mutations, including dominant lethals (of a special type). The claim that a reduction in dose rate lowers the yield of mutations following gonial irradiation in the male mouse has so far not been confirmed by studies on Drosophila . Primary meiocytes are relatively insensitive to cell‐killing. Cells irradiated as spermatocytes may fail, or be slow to complete normal maturation division(s), or they may give rise to morphologically abnormal spermatids. The effect depends upon the phase of meiosis at irradiation. In both sexes, sensitivity to cell‐death appears to decrease more or less progressively as meiotic prophase advances; in most female mammals, the trend is sharply reversed at early diplotene, when the oocytes become enveloped within primordial follicles. As the oocyte enters upon its rapid phase of growth which, in many species, is associated with vitellogenesis, sensitivity decreases again. Growing oocytes at the diplotene stage are relatively resistant to cell‐killing in almost all species investigated. Due to the brief duration of subsequent stages of meiosis (diakinesis, metaphase I), sensitivity to cell‐death is difficult to establish. As judged by the induction of dominant lethals, sensitivity of oocytes increases sharply between diplotene and metaphase I; in rodents, the rise becomes manifest a few hours before the onset of diakinesis. Increases of the same magnitude in the incidence of chromosomal aberrations at anaphase I and II have been scored for microsporocytes. Corresponding data for spermatocytes are less reliable, but there is some evidence indicating the same trend. In general, sensitivity to the induction of mutations is greater in meiocytes than in gonia. The yields of some mutations in the female have been shown to rise as meiotic prophase proceeds; but the relative increase as metaphase I approaches is not always as striking as that recorded for dominant lethals. Differential sensitivity to mutagenesis in spermatocytes at various stages of meiotic prophase has not been fully documented. There is some reason to believe that spermatocytes at early stages of meiotic prophase are less susceptible to mutation induction than those nearing the end of prophase. The sensitivity of secondary meiocytes has not been quantitatively assessed except by the incidence of chromosomal aberrations and dominant lethality. In both plants and animals, cells at metaphase II appear to be somewhat less sensitive than those at metaphase I. Spermatids, whose homologous stage is absent in the female, are apparently highly resistant to the induction of morphological abnormalities or cell‐death, In contrast, they are highly sensitive to the induction of dominant lethals and a variety of mutations; those at early stages of spermiogenesis appear to be more susceptible than those approaching full differentiation. Corresponding changes are less readily induced in fully differentiated spermatozoa. Anoxia during irradiation diminishes the difference between spermatids and spermatozoa, without however abolishing it. Spermatozoa irradiated after insemination are more sensitive to mutagenesis than are those retained within the testes or the male genital ducts. Irradiation of differentiated gametes of either sex shortly before fertilization induces a delay in subsequent cleavage. While eggs undergo some spontaneous recovery if the period between irradiation and fertilization is prolonged, spermatozoa do not. There is at present no single working hypothesis to account for all the stage differences recorded.