Effect of gamma radiation at high- and low-dose rate on a novel in vivo mutation assay in mouse intestine

Mutagenesis. 1989 Sep;4(5):404-6. doi: 10.1093/mutage/4.5.404.

Abstract

We have previously proposed that an in vivo mutagenicity assay could be based on the detection of mutations affecting the Dlb-1 locus in the small intestine of C57BL/6J x SWR F1 mice. F1 mice are heterozygous Dlb-1b/Dlb-1a and have only a single allele (Dlb-1b) which specifies expression of the binding site for the lectin Dolichos biflorus agglutinin (DBA) in intestinal epithelia. In whole-mount preparations of small intestine stained with a DBA--peroxidase conjugate, mutated stem cells and their progeny can be recognized as ribbons of unstained cells against a stained background. These DBA-negative ribbons can be quantified. The present investigation characterizes the responses of F1 mice to high- and low-dose rate gamma radiation (1.8 and 0.01 Gy/min respectively) and shows that the induction of ribbons is dose dependent in both cases. Dose sparing is evident at the lower dose rate: 20 ribbons/10(4) villi can be induced by 4 Gy at high-dose rate and by 7.1 Gy at low-dose rate, a dose sparing of 1.76. Age-matched untreated mice had a background level of 3.7 ribbons/10(4) villi. As expected, no ribbons were observed in homozygous (Dlb-1b/Dlb-1b) C67BL/6J mice, in which each stem cell has two alleles specifying lectin binding. The results further validate this system as a sensitive in vivo mutagenicity assay and suggests that the target cells are capable of repairing radiation damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Radiation
  • Gamma Rays
  • Intestines / radiation effects*
  • Mice
  • Mutagenicity Tests*
  • Mutation*
  • Whole-Body Irradiation