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Experimental Chemotherapy Studies. VII. The Effect of Alkylation on the in Vitro Thymidine-Incorporating System of Lettré-Ehrlich Cells^*

( Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania)

In vivo nitrogen mustard treatment of sensitive Ehrlich ascites tumors results in a profound inhibition of in vitro thymidine-H³ (TdR-H³) incorporation. Approximately two-thirds of this effect can be traced to inhibition of the TdR-H³-incorporating enzyme system and one-third to inhibition of the primer activity of the nuclear fraction, indicating that the nitrogen mustard lesions can be both cytoplasmic and nuclear in nature. Examination of various alkylated DNA preparations shows that the inhibition of primer activity is due not to alkylation of DNA per se, but to some more complex in vivo relation, probably involving the residual protein retained by DNA after alkylation and purification.

^* This research was supported by United States Public Health Service Grant CA-05295-04.

Received 2/24/64.