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Enhancement of the anticancer activity of bis(2-chloroethyl)nitrosourea in mice by coadministration of 2'-deoxyuridine, 2'-deoxycytidine, or thymidine.

Abstract
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 greater than 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 non-thymidine-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.
AuthorsT S Lin, W H Prusoff
JournalCancer research (Cancer Res) Vol. 47 Issue 2 Pg. 394-7 (Jan 15 1987) ISSN: 0008-5472 [Print] United States
PMID3791229 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Deoxyribonucleosides
  • Ribonucleosides
  • Deoxycytidine
  • Carmustine
  • Thymidine
  • Deoxyuridine
Topics
  • Animals
  • Carmustine (administration & dosage)
  • Deoxycytidine (administration & dosage)
  • Deoxyribonucleosides (administration & dosage)
  • Deoxyuridine (administration & dosage)
  • Drug Synergism
  • Leukemia L1210 (drug therapy)
  • Melanoma, Experimental (drug therapy)
  • Mice
  • Ribonucleosides (administration & dosage)
  • Thymidine (administration & dosage)

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