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FP5

Genetic factors predisposing to radiation induction of mutation during early gestation: the role of DNA repair and cell-cycle control (GEMRATE), Final report (summary)

Project ID: FIGH-CT-2002-00210
Funded under: FP5-EAECTP C

Abstract

The purpose of GEMRATE was to provide an increased insight into the risks of the sperm, zygote, and post-implantation gastrula stages for mutation induction after ionising irradiation.
Human conceptions are for a substantial part not planned. And if pregnancy occurs, many women at the time of post-implantation gastrulation do not realise they are pregnant. Therefore, knowledge about the genetic vulnerability to irradiation at this stage is needed, but also for the following reasons it deserves more attention.
When during spermiogenesis, the haploid nucleus condenses for which an all-over chromatin change is mandatory, a DNA repair system is no longer available. Also, radiation-induced nuclear damage does no affect the fertilising capacity of the sperm, i.e. selection against a DNA-damaged male gamete is absent. This stage is of variable duration in the human, depending on the transport and storage of the sperm in the epididymis, and could last from one to up to four weeks. Gastrulation in the human embryo occurs after implantation and takes place in the second and third weeks of development.
After fertilisation, DNA damage of the sperm is detected by the zygote and processed by the cytoplasm of the zygote, constituting a maternal effect. The interaction between paternal damage and zygote cytoplasm will determine the fixation of mutations. The role of the zygote in karyotype evolution is not officially known but very likely.
The zygote stage has a short duration, but from the onset of radiation genetics, it has been known that the early to mid zygote is extremely sensitive to ionising radiation. Radiation sensitivity of the gastrula is blank terrain, but a first warning publication was published in 2000, suggesting that by its extreme apoptosis sensitivity, the gastrula rids itself from illbehaving cells. In GEMRATE we have tried to develop a technical and biological-conceptual fundament for radiation genetics and gastrula development.

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Record Number: 8953 / Last updated on: 2008-02-13
Category: PRJS
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