The development of the 30 to 40% deficiency in DNA synthesis in HeLa S3 cells in the generation (Generation 1) after the one in which they were irradiated in G1 with 500 rads of 220 kV x-rays was examined. Incorporation of thymidine immediately after reversal of FUdR blockade at the beginning of the S phase in Generation 1 and immediately after reversal of puromycin inhibition of protein synthesis in mid-S of Generation 1 appears to be unaffected by radiation. The reduced synthesis is progressively manifested as synthesis proceeds; after reversal of both FUdR and puromycin inhibition, maximum reduction is reached in 10-15 min. In independent experiments involving inhibition of protein synthesis in unirradiated cells, this interval is shown to be the average time required for maximum inhibition of DNA synthesis. RNA synthesis in Generation 1 is reduced, but only after S phase has begun. A working model is proposed to account for the deficient synthesis in Generation 1. It is postulated that the DNA strand complementary to the strand with the initial damage is replicated with a lesion opposite that damage, and that replication of this strand in Generation 1 results in deficient synthesis.

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