Nature and consequences of induced chromosome damage in mammals.

There are marked qualitative and quantitative differences in the patterns of chromosomal damage observed after irradiation of spermatogonia, spermatozoa and oocytes of mice. These differences often result from reduced or zero transmission of particular classes of abberration arising in pre-meiotic germ cells. Probably this is the reason why the level of X-chromosomal and autosomal monosomy is not increased after spermatogonial irradiation. Similarly, the reduced transmission of certain d-se deficiencies may help to explain their low F(1) frequency after pre-meiotic as compared with later irradiation. Spermatozoal irradiation has revealed no Robertsonian translocations, but has produced some types of reciprocal translocations which apparently are not transmitted to the F(1) after spermatogonial treatment because they prevent maturation of the male pre-meiotic germ cell. Thus they cause sterility in males, but not in females. They include X-autosome and Y-autosome translocations, those giving a metacentric or sub-metacentric chromosome (with reciprocal product present) and those in which one break-point is in or near the centromeric heterochromatin while the other is more distally placed. This last group (which grades into male sub-fertile conditions) gives a preponderance of chain configurations (often with one separate univalent) in heterozygotes of both sexes at meiosis and a high incidence of somatic marker chromosomes. Nondisjunction associated with the univalent generates tertiary trisomics, which are usually male-sterile also and may show phenotypic abnormalities. Sterile males with complete separation of X and Y chromosomes have also been reported after mutagenic treatment of meiotic and post-meiotic germ cells. Such separation seems to prevent a primary spermatocyte from forming a secondary one. The usual derivation (in mouse and man) of tertiary trisomics from mothers rather than from fathers may be due to a similar block, together with a general tendency for male heterozygotes for the parental balanced translocation to be sterile or sub-fertile. Mature oocytes tend to resemble spermatoza in the types of aberration produced by irradiation, which include the male-sterile translocation, but more data are needed. Many of the aberrations described contribute to the human cytogenetic load and can be studied in the mouse from this point of view.