BUdR

Date:
1970
Reference:
PP/CRI/H/4/18
Catalogue details

Licence: In copyright

Credit: BUdR. Source: Wellcome Collection.

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    Notes on a discussion with Howard Holtzer - 31 July 1970 (plus some later remarks) 1. Effects of BUdR at different levels At very low concentrations, 3 x 10 ^M, fusion is prevented. At intermediate concentration, e.g. 1.6x10 ^M, muscle is not produced. -4 At higher concentrations, e. g. 1. 6 x 10 M, the cells reproduce more slowly, either because the division cycle takes a longer time, or because of cell death. Nevertheless, they can grow in this concentration for a considerable _3 time. Higher concentrations (? x 10 M) are toxic. This suggests to me that at the higher concentrations the BUdR is making errors in protein sequences. This could be because the BUdR in the DNA occasionally puts G into RNA (mRNA, rRNA or tRNA) instead of A. The rate for this process is unknown. It could be higher than the rate of making -3 -4 mutations in DNA. A guess at the rate might be 10 to 10 . Obviously the effects of this are difficult to estimate, since it depends both on the turnover- time of the RNA, and also the turnover-time of the protein being considered. However, the effects would probably be cumulative, but might plateau after, say, several generations. The problem is also complicated by the possibility of selective cell death. Moreover, in certain cases if a certain amount of dud protein is produced the regulatory mechanisms may in some cases turn up the gene to produce more total protein (for that gene) until the normal activity level is reached. Consequently the demonstration that the level of a particular enzyme is altered very little does not necessarily mean that no dud