Recent reports in the mouse indicate considerable radiation sensitivity of particularly the early zygote and the post implantation gastrula stages. Data on the chromatin stability of human sperm and chromosome stability of pre implantation embryos point at the genetic vulnerability of these stages in our species. We propose to assess, for the mouse, the roles of single and double strand DNA break repair and cell cycle control at the zygote and gastrula stages in response to radiation-caused DNA damage of male post meiotic haplophase stages, the zygote- and gastrula stages. Various genetic, cell cycle and developmental endpoints will be utilised to understand the importance of DNA break repair and cell cycle control for the transmission of genetic damage for sperm, zygote and gastrula stages, such that risk assessment and mechanistic insight are coupled. By including transcriptome analysis, DNA damage response genes can be identified.
Funding SchemeCSC - Cost-sharing contracts
2300 RA Leiden
LE1 7RH Leicester