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- W2138843258 abstract "Abstract Antifolates cause cells to accumulate exogenous UdR as dUMP in drug-treated cells. This accumulation of intracellular dUMP has no effect on inhibition of UdR incorporation into DNA. On the other hand, dUMP accumulation does result in detectable dUTP being synthesized and utilized as substrate for DNA synthesis. Although in the presence of metoprine (DDMP), dUMP is incorporated into DNA instead of TMP, the natural product of UdR substrate in the absence of the drug, DNA synthesis is equally rate limited by exogenous UdR. However, when analyzed on alkaline sucrose gradients, DNA which has incorporated exogenous UdR in the presence of antifolate sediments at 4S or less. This newly synthesized DNA accumulates preferentially while either synthesis of larger DNA is blocked, or high molecular weight DNA is preferentially broken down as a result of DNA repair. These observations further increase the metabolic complexity of pathways that must be considered as underlying the differential toxicity of antifolates." @default.
- W2138843258 created "2016-06-24" @default.
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- W2138843258 date "1981-01-01" @default.
- W2138843258 modified "2023-09-27" @default.
- W2138843258 title "An antifolate-induced lesion in newly synthesized DNA" @default.
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- W2138843258 doi "https://doi.org/10.1016/0065-2571(81)90021-2" @default.
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