Induction of translocations in mouse spermatogonia after fractionated exposure to 60Co gamma-rays

Male mice of the Q strain were exposed to 60Co gamma-rays at 2 Gy and 2 X 2 Gy separated by increasing time intervals (from 0 min to 4 min). The chromosome translocations induced in spermatogonia were scored at diakinesis-metaphase I. A significant decrease of the translocation frequency at time intervals higher than 2 min was observed, confirming results obtained with plant materials.     

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

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)     

Cytogenetic effects of fractionated or unfractionated X-ray exposures to mouse spermatogonia

The induction of chromosomal aberrations in mouse spermatogonia was studied, after single (50 and 100 rad) and fractionated doses (50 + 50 rad spaced 24 h apart), a short time after irradiation, by analysis of mitotic stages. From 17 to 21 h after the second fraction of the dose, the recorded frequencies of chromosomal deletions and exchanges were fully additive when compared with single “control” doses. Thus there was no suggestion of any sensitization effect of the first exposure. Possible reasons for this are discussed.     

Response of mouse small intestine to fractionated doses of pions

The effect of single or fractionated doses of stopping pions or 200 kV X-rays on the mouse jejunal crypt cells was used to determine in vivo RBE values. For single fraction, the pion/X-ray RBE was 1.27 and it increased to about 1.31 when two fractions were applied at 3 or 24 h interval. When four fractions were given at 3 h intervals, the RBE was 1.46. This is because the fraction of "dose repaired" was always higher for X-rays than for pions and this difference was enhanced when more dose fractions were used. The data presented is, in general, consistent with the biological effects of pions reported for other in vivo end points.     

The effects of the time interval in fractionated x-ray treatment of mouse spermatogonia

Male CBA strain mice were submitted to fractionated radiation treatment of spermatogonia. Effects of doses of 300 R + 300 R, 400 R + 400 R and 500 R + 500 R with time intervals of 24, 48, 72 and 144 h between irradiations were studied.     

Relative biological effectiveness of x-rays and fast neutrons in inducing translocations in mouse spermatogonia

The dose-response relationships for inducing translocations in the spermatogonia of mice were studied, and they were compared for 200 kVp X-rays and 2 MeV fast neutrons. The dose response for fast neutrons was markedly convex; more precisely, the response obtained was linear in the dose range from 24 to 94 rad with a regression coefficient of 11.36·10^?4, but decreased for a further increase in dose up to 267 rad. On the other hand, that for X-rays showed a linear dose-response relationship from 48 to 672 rad with a regression coefficient of 2.69·10^?4. The relative biological effectiveness for inducing translocations in the spermatogonia of mice was compared for the linear parts of the dose response in both types of radiation, and the relative biological effectiveness (RBE) value was 4.22.     

Serial analysis of chromosomal aberrations and proliferation kinetics of mouse spermatogonia after single or fractionated X-ray exposures

Dose-fractionation studies on translocation induction in stem-cell spermatogonia of mice, as measured by spermatocyte analysis many cell generations after irradiation, revealed that a small conditioning dose of X-rays sensitizes the stem cells to the induction of translocations by a second dose 24 h later (Van Buul and Léonard, 1974, 1980). To find out whether such sensitization effects also occur at other spermatogonial stages, a comparison was made of the effects of single (50, 100 and 150 rad) and fractionated (100 + 50 rad, with 24 h in between) doses of X-rays on the induction of chromosomal aberrations in spermatogonia by analysing spermatogonial metaphases shortly after irradiation at multiple sampling times (0–48 h; every 4 h). In addition, the kinetics of spermatogonial proliferation was studied by using, in vivo, a BrdU chromosome-labelling procedure. The recorded frequencies of chromosomal aberrations did not indicate any sensitization effect of dose fractionation. It is concluded that the sensitization effects, as observed for chromosomal aberrations in male premeiotic germ cells, are characteristic for the stem-cell spermatogonia and do not occur in the more differentiated spermatogonia.     

Chromosome modifications induced in mouse spermatogonia through exposure to high-energy neutrons]

The incidence of reciprocal translocations induced in mouse spermatogonia has been studied in CBA mice given X-ray or neutron exposure. Analysis of dividing spermatocytes at diakinesis-first metaphase stage of meiosis shows that in X-irradiated mice there is a linear dose-response relationship. After exposure to fast neutrons the yield of translocations follows a humped curve with a maximum of chromosome exchanges after exposure to 100 rad.