BUdR Calculations

Date:
1970
Reference:
PP/CRI/H/4/19
Catalogue details

Licence: In copyright

Credit: BUdR Calculations. Source: Wellcome Collection.

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    orated before an inhibition of red cell differentiation is ob served; consequently, the mechanism that 'reads' the DNA probably interacts with both strands of the double helix. Embryos treated at 5 hours display an even greater amount of inhibition at the lower doses. This is again correlated with the estimated number of divisions prior to overt differentiation at 35 hours; thus, in general, increasing the number of divisions in ErdUrd leads to a proportional decrease in the fraction of red cells differen tiating. This lends further support, but not proof, to the idea that BrdUrd must act through the DNA for it to have an effect on differentiating cells. It is possible that erythropoiesis involves two successive BU sensitive steps between 15 hours and 35 hours. If this were the case then the slope of the 15 hour curve should be much steeper than that of the 25 hour curve assuming both steps were of comp arable sensitivity. Since this is clearly not the case, it is most probable that the BU sensitive step in erythropoiesis occurs at about 35 hours when the cells are about to commence the synthesis of Hb. There is not sufficient data to say if there is a BU sensitive step before 15 hours. The extrapolation number of 9 is intriguing, yet subject to several explanations. The following argument is consistent with the results, but is by no means the only interpretation, nor should it be considered such. Assume that 9 hits per diploid cell is equivalent to about 5 hits per haploid genome, or, equivalently, both alleles in homologous chromosomes must be inactivated by BrdUrd before an affect on differentiation can be observed. If 5 represents 5 hits per target and one target per haploid set of chromosomes then theory would predict that the slopes shown in apparent Fig.l be curved. The/linearity of the 15 and 25 hour'.slopes argues against this type of multi-hit, single target mechanism