Stage specificity, dose response, and doubling dose for mouse minisatellite germ-line mutation induced by acute radiation

Abstract

Germ-line mutation induction at mouse minisatellite loci by acute irradiation with x-rays was studied at premeiotic and postmeiotic stages of spermatogenesis. An elevated paternal mutation rate was found after irradiation of premeiotic spermatogonia and stem cells, whereas the frequency of minisatellite mutation after postmeiotic irradiation of spermatids was similar to that in control litters. In contrast, paternal irradiation did not affect the maternal mutation rate. A linear dose-response curve for paternal mutation induced at premeiotic stages was found, with a doubling dose of 0.33 Gy, a value close to those obtained in mice after acute spermatogonia irradiation using other systems for mutation detection. High frequencies of spontaneous and induced mutations at minisatellite loci allow mutation induction to be evaluated at low doses of exposure in very small population samples, which currently makes minisatellite DNA the most powerful tool for monitoring radiation-induced germ-line mutation.

Figure 1

Mutation induction at minisatellite loci in mice. (a and b) Frequencies of paternal and maternal mutation in offspring conceived 3, 6, and 10 weeks after paternal irradiation by 1 Gy of x-rays (a, aggregated data; b, frequency of mutations in each family). (c and d) Dose–response curves for minisatellite mutations induced in premeiotic cells. (c) Aggregated data. (d) Frequency of paternal mutation in each family (r = 0.6131; P = 2.0 × 10⁻⁵ and r = 0.0888; P = 1.0000 for the arcsine-transformed values of paternal and maternal mutation rates, respectively. Values of Bonferroni probabilities for the coefficients of correlation are given). Dashed lines indicate 95% confidence intervals for the linear regression. The 95% confidence intervals for mutation rate, estimated from the Poisson distribution and probabilities of difference between paternal and maternal rates (Fisher’s exact test, two-tailed) are shown for aggregated data.