Determination of the Mode of Action of 5/6-Dihydro-5-Azathymidine
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A study has been made to elucidate the mode of action of a new antibiotic, 5,6-DIHYDRO-5-AZATHYMIDINE. This drug has been found to cause a phenomenon described in the literature as "thymineless death". Our studies have shown that DhaT does, in fact, cause a loss of thymidine available for DNA synthesis as opposed to inhibition of DNA polymerase. This decrease in available TTP is shown to be due to a decrease in intercellular TMP. This loss of TMP is not due to inhibition of thymidylate synthetase activity, however. Rather, it is shown that there is an increased drain on the TMP pool by thymidine kinase.