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Blood Thymidine Level and Iododeoxyuridine Incorporation and Reutilization in DNA in Mice Given Long-acting Thymidine Pellets¹

Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111 [W. L. H.]; Oncology Center, Johns Hopkins Hospital, Baltimore, Maryland 21205 [D-J. L.]; Sloan-Kettering Institute, Section 6001, New York, New York 10021 [W. P.]; and School of Pharmacy, Northeastern University, 113 Mugar Building, Boston, Massachusetts 02115 [G. K.]

A long-acting thymidine pellet consisting of 190 mg of cholesterol and 60 mg of thymidine has been developed for the study of thymidine metabolism and reutilization in vivo. Implantation of such a pellet s.c. in adult mice will maintain the blood plasma concentration of thymidine at levels between 40 and 8 x 10^-6 M, which are from 36 to 7 times those of normal mice, for periods up to 48 hr. During this period, in vivo uptake and reutilization of [¹²⁵I]iododeoxyuridine, a thymidine analog, into intestinal and tumor DNA were almost completely suppressed. While iododeoxyuridine reutilization is not large in normal proliferative tissue even in the absence of pellet implants, reutilization of over 30% was measured in large, rapidly growing ascites tumors. The inhibition of iododeoxyuridine incorporation by elevated thymidine blood levels is directly proportional to serum concentration. This appears to be due to a thymidine pool in rapid equilibrium with blood thymidine. This pool is at least 10 times larger than the 4-nmole pool of extracellular thymidine.

¹ This work was supported by Grant CA-10734 from the National Cancer Institute.

Received 3/31/76. Accepted 8/16/76.

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