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Studies on Unbalanced Growth in Tissue Culture

I. Induction and Consequences of Thymidine Deficiency^*

( McArdle Memorial Laboratory, University of Wisconsin Medical School, Madison, Wis.)

Thymidine-deficient growth of HeLa cells induced by either of two agents, amethopterin or 5-fluorouracil-2'-deoxyriboside, resulted in an unbalanced growth syndrome strikingly similar to that described for bacteria. Thus, mitosis and DNA synthesis were blocked while RNA and protein synthesis continued.

After an interval of thymidineless growth corresponding to about two-thirds of a generation, the cells abruptly began to lose their capacity to reproduce progeny at a rate of 90–99 per cent per generation. At about the same time the rate of RNA accumulation fell rapidly and after 24 hours ceased completely. Protein continued to accumulate only very slowly under such conditions. Such results are in accord with the hypothesis that thymidineless death represents a nuclear inactivation.

Restoration of thymidine after a suitable interval of deficient growth resulted in synchronous division of these cells. The growth kinetics of such cultures is described, and evidence suggesting a multiple role of thymidine or its derivative(s) in cellular reproduction is presented.

^* This work was supported by a grant from the Alexander and Margaret Stewart Trust Fund, Grant No. CY-1897(C7), from the United States Public Health Service, and a grant from the T. Evans Brittingham Estate.

Received 6/16/60.

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