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Marker chromosome analysis of 18 tetraparental AKR↔CBA/H-T6 chimaeras revealed a great excess of AKR mitoses over CBA mitoses in direct preparations from lymphomyeloid tissues, corneal epithelium, intestinal epithelium and skin (Table 1). The degree of AKR dominance was strongly influenced by anatomical site (Tables 2 and 3). The testes of three out of four XY/XY males contained a marked excess of AKR germ cells and produced a parallel excess of functional AKR gametes (Table 4). Mitotic spreads in mitogen-stimulated cultures of tail blood were overwhelmingly of AKR type in 1972, but less so in 1973 (Table 5). The coat phenotypes, and breeding results from known or presumptive XX/XX females, suggest that AKR and CBA cells were numerically balanced when melanoblasts and oocytes were formed during embryonic development, and therefore that the striking deviations from equality observed in mitotic populations of adult chimaeras arose later by differential proliferation or survival of AKR cells, or both. The low frequency of lymphomas, compared with normal AKR mice, previously reported in these chimaeras cannot therefore be accounted for by insufficiency of AKR cells in the thymus or elsewhere in the lymphomyeloid tissues. One of three lymphomas studied was CBA type. This suggests that the high risk of lymphomatous transformation is not an autonomous property of AKR cells.

The karyotype analysis of a mentally retarded baby with persistence of embryonic and foetal haemoglobin showed three abnormal chromosomes. One was identified as a No. 3 with an extra segment, another as No. 6 or 7, or X, with a deletion and the last one was assigned to pair 15 by autoradiography. The parents of the propositus were both haematologically and chromosomally normal. The possible mechanisms of origin of the multiple chromosomal rearrangements arc discussed. The data are also compared with those reported by other authors in connection with different chromosomal abnormalities. Particular attention is paid to trisomy D, which has been found associated with persistence of foetal haemoglobin. Although the possibility of a nonspecific effect of the observed karyotypic alterations cannot be ruled out, the suggestion is made that one or more of the abnormal chromosomes are carriers of gene(s) controlling the synthesis of e and γ chains.

Translocation frequencies were studied in spermatocytes derived from the spermatogonia of mice given 300 rad X-rays in two equal fractions separated by intervals of 0–8 h. In the first experiment (0–2 h intervals) there was a significant fall from 14.5% to 8.1% in the frequency of affected cells when there was an 0.5-h interval between doses instead of a single dose, followed by a just significant rise to 10.8% at a 2-h interval. However, the translocation frequency after a single 300-rad dose was higher than expected from previous experiments at this level (see paper III of this series). In the second experiment (0–8 h intervals) there was again an initial fall (from 8.8% at 0 h to 6.6% at 1 h) and a rise later (to 8.1% at 6 h and at 8 h intervals), but the changes in frequency did not reach a significant level. Results are compared with those obtained in similar recent experiments by Leonard and Deknudt (500 R total exposure) in which an initial decrease in yield was also found, but with more pronounced fluctuations in frequency later. The relative importance of radiation-induced changes in the spermatogonial population and of decreased oppurtunities for interaction of lesions on fractionation is discussed with reference to the observed effects.

The effect of dose-rate on the induction of reciprocal translocations in mouse A type spematogonia by 600 RX- and γ-irradiation was studied by scoring multivalent configurations in descendant spermatocytes. With X-irradiation over a range of dose-rates from 0.8 to 913 R/min there was no significant change in the frequency of affected spermatocytes, which averaged 12.8%. With γ-irradiation, however, there was a steady increase in frequency from 1.4% at 0.02 R/min to 12.1% at 86 R/min, the points fitting a straight line on a semi-log plot. At 0.08 R/min the X-ray yield was twice that for γ-rays. Possible reasons for these differences are discussed. Frequencies of 0, 1, 2 translocations per spermatocyte did not fit a Poisson distribution since there were less then expected in the 1-class, but more in higher classes. This was probably a consequence of differential radiosensitivity of the irradiated spermatogonia, although preferential clonal proliferation may also be involved.

Translocation frequencies were studied in mouse spermatocytes derived from X-irradiated spermatogonia. Over the range from 50–800 R the dose-response relationship did not differ significantly from linearity, in agreement with previous findings of Leonard and Deknudt . It seems probable that the initial dose-response curve has the expected square-law component but becomes destorted by secondary factors between irradiation and meiotic examination of cells. Observed translocation frequencies were little affected by increasing length of time (from 11–30 weeks) between irradiation and examination, except for a possible decline at the highest dose (800 R). No significant frequency differences were found between mated and solitary males, or between those given whole-body or part-body (gonadal) irradiation.

Publisher Summary This chapter describes the selection pressure in mammalian cell populations. Mammalian cells offer a limited population genetics of their own, analogous to the population genetics of sexually reproducing organisms, though obviously less complex. The frequency of hyperdiploidy may be of the order of one in 1000 and the frequency of structural rearrangement is much lower. The frequency of hypodiploidy cannot be objectively estimated at all because of confusion with spuriously low counts resulting from cell breakage. An approach that could demonstrate a proliferative differential between normal cells and aneuploid cells is offered by the occurrence of karyotypic mosaics in man.