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 Jaffe, J. J. Articles by Cooper, J. R. Search for Related Content PubMed PubMed Citation Articles by Jaffe, J. J. Articles by Cooper, J. R.

Studies on 6-Uracil Methyl Sulfone

II. Anti-Tumor Activity

( Department of Pharmacology, Yale University School of Medicine, New Haven, Conn.)

6-Uracil methyl sulfone (UMS) inhibited the growth of lymphomas L1210 and L5178-Y to a significant degree when injected subcutaneously, but only at concentrations which were toxic to the tumor-bearing mice. Under the same conditions, UMS did not significantly inhibit the growth of Sarcoma 180.

UMS exhibited no antitumor activity when administered orally, although the average intake of the drug by this route was greater than the maximally effective parenteral dose. The drug also exerted no antitumor activity when injected once rather than thrice daily, although the single daily dose was equivalent to the sum of three divided daily doses.

Metabolic studies on UMS revealed that a variety of mouse tissues are capable of altering the compound extremely rapidly. The exceptions observed were blood and various tumors (L1210, L5178-Y, and S-180). In addition, it was found that in S-180 growing in mice receiving UMS parenterally, the ratio of unaltered compound to metabolite was greater than one, while the reverse was true when the tumor was growing in mice receiving UMS orally. From these studies, and because of the very high activity of UMS as an inhibitor of the reproduction of cells in culture (observed by Fischer), the conclusion was reached that unaltered UMS is responsible for both antitumor activity and host toxicity.

The results of acute and chronic toxicity studies of UMS in mice are presented.

Received 5/29/58.