The incidence of sex-chromosome anomalies following irradiation of mouse spermatogonia with single or fractionated doses of X-rays

Abstract

Attempts to recover XO offspring resulting from 600 R irradiation of spermatogonia proved negative. X-Rays were administered either in a single dose or in 100+ 500 R fractions separated by 24 h, and controls were strictly comparable in all respects. Altogether 14016 offspring were scored, including a small group derived from irradiated mature spermatozoa. The breeding scheme allowed phenotypic detection of paternal or maternal sex-chromosome loss, paternal nondisjunction, and certain translocations. All phenotypically exceptional mice were examined cytologically and through breeding tests. Similar tests of the mothers of presumed O/X p exceptionals revealed that in 9 of 14 cases there was a pre-existing XO condition, indicating the importance of performing such a test. Two of the 3a X m /O-appearing mice were probably X m /O///X m /X p mosaics, with the integument predominantly XO and the germinal tissue predominantly X/X. The frequency of paternal sex-chromosome loss was 2.4 · 10 −3 in the controls and 2.0 · 10 −3 in the two irradiated groups, where X m /O's must therefore be assumed to be of spontaneous origin. Since translocation experiments provide evidence that chromosome breaks are induced by irradiation of spermatogonia, the failure to recover XO's is explained in one of two possible ways. (1) Breakage in spermatogonia does not lead to recoverable single-chromosome loss, either because no sister-chromatid joining occurs, or, if it does, because this leads to cell-division failure. (2) Alternatively, sex chromosome loss does occur, but resulting X/O and O/Y cell progeny is inviable in the testis—a suggestion supported by evidence from natural and artificial mosaics. The results of the present experiment lend further support to our earlier suggestion that most spontaneously occurring X m /O mice are the result of events occurring after sperm entry into the egg. The spontaneous frequency of paternal sex-chromosome loss has ranged over two orders of magnitude in various reports. On the other hand, the frequencies of spontaneous X m loss (O/X p daughters of X/X females/total daughters) and of paternal nondisjunction (2 · X m /X p /Y frequency)