Prediction of antifolate efficacy in a rat sarcoma model

Wei Wei Li, James T. Lin, Y. M. Chang, Barry Schweitzer, Joseph R. Bertino

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

A methylcholanthrene‐induced rat sarcoma propagated both in vitro and in vivo was used to examine the usefulness of a rapid biochemical in situ assay that measures thymidylate synthase (TS) activity in whole cells to predict sensitivity and resistance to the folate antagonists methotrexate (MTX), 10‐ethyl‐10‐deazaaminopterin (10‐EDAM) and trimetrexate (TMTX). There was an excellent correlation between the effects of these drugs on inhibiting TS and cytotoxicity as measured by a clonogenic assay, when the exposure time was 4 hr, and those when the rat sarcoma cell line was employed (p < 0.001). When tumor‐cell suspensions were prepared from the rat sarcoma propagated in vivo, they were less sensitive to these antifolates, but the relative effectiveness of the 3 antifolates was similar: TMTX ≫ 10‐EDAM > MTX. As expected, continuous exposure (10 to 12 days) produced cytotoxicity at a much lower dose of these drugs. When the 3 drugs were tested for anti‐tumor effectiveness in rats bearing this tumor, the tumor regression measured was best with TMTX; 10‐EDAM was intermediate in effectiveness as compared with MTX. These results indicate that the in situ TS assay and clonogenic assay may be used to predict anti‐tumor efficacy of antifolates in vivo in this rat sarcoma.

Original languageEnglish (US)
Pages (from-to)234-238
Number of pages5
JournalInternational Journal of Cancer
Volume49
Issue number2
DOIs
StatePublished - Sep 9 1991

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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