Tests of induction in mice by acute and chronic ionizing radiation and ethylnitrosourea of dominant mutations that cause the more common skeletal anomalies

Abstract

Assessment-of-Dominant-Damage (ADD) experiments explored induction by proven specific-locus mutagens of dominant mutations that cause skeletal anomalies, cataracts, and stunted growth in offspring of mutagenized male mice. The data set reported here includes 6134 offspring. Mutagenic treatments included 600 R (i.e., approximately 6 Gy) of X-rays delivered in about 7 min, 600 R of gamma rays delivered over about 110 days, and four weekly intraperitoneal (i.p.) injections of 77.5 mg/kg of ethylnitrosourea (ENU). The results reported in this paper are restricted to mutations induced in stem-cell spermatogonia and to the 34 more common skeletal anomalies (i.e., those found in 0.5% or more of the control offspring). Mutation induction was demonstrated for eight anomalies in the acute X-ray experiment and for 17 anomalies (including those same eight anomalies) in the ENU experiment. In spite of the surprisingly high mutation rates found for these treatments, there was no hint of any induction of such dominant mutations by 600 R of chronic gamma radiation. Our results suggest that several anomalies related to variation in the sacralization pattern may be particularly useful for revealing induction of dominant mutations.