This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lin, T.-S. Articles by Prusoff, W. H. Search for Related Content PubMed PubMed Citation Articles by Lin, T.-S. Articles by Prusoff, W. H.

Enhancement of the Anticancer Activity of Bis(2-chloroethyl)nitrosourea in Mice by Coadministration of 2'-Deoxyuridine, 2'-Deoxycytidine, or Thymidine¹

Department of Pharmacology and Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510

The previous observation that the coadministration of a single dose of thymidine with the 3'-chloroethylnitrosourea analog of thymidine (3'-[3-(2-chloroethyl-3-nitrosoureido]-3'-deoxythymidine, 3'-CTNU) to mice bearing the L1210 or P388 leukemia enhanced the antitumor activity of 3'-CTNU, has led to a similar study of the potential effect on antitumor activity where thymidine, 2'-deoxyuridine, or 2'-deoxycytidine is coadministered with 1,3-bis(2-chloroethyl)-1-nitrosourea. Three levels of 1,3-bis(2-chloroethyl)-1-nitrosourea (10, 15, and 20 mg/kg) were coadministered to mice bearing the L1210 leukemia or the B16/F10 melanoma with each of the deoxyribonucleosides (2 g/kg). There was not only an increase in average days of survival of those that perished, but also a marked increase in the number of >60-day survivors.

The present report is a result of a determination of whether the augmented anticancer activity produced by a single injection of thymidine with 3'-CTNU was restricted to nitrosourea analogs of thymidine. The present study reveals not only that the phenomena of enhanced anticancer activity by the coadministration of thymidine can be extended to nonthymidine-containing nitrosoureas, but also that the coadministration of thymidine with 1,3-bis(2-chloroethyl)-1-nitrosourea produced an even more marked enhancement of antitumor activity than that previously observed when thymidine was coadministered with 3'-CTNU.

¹ This investigation was supported by Grant CH-115 from the American Cancer Society.

² To whom requests for reprints should be addressed, at the Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, P.O. Box 3333, New Haven, CT 06510.

Received 6/24/86. Revised 9/15/86. Accepted 10/ 9/86.