Abnormal deoxyuridine suppression as a rapid predictor for antimetabolite chemosensitivity: correlation with in vitro tests of growth inhibition.
The deoxyuridine (dU) suppression test, which estimates the activity of the de novo pathway to DNA synthesis from dU, was evaluated as a predictor of antimetabolite growth inhibition. Observations of growth inhibition were made using flask cell culture and soft agar clonogenic assay and correlated with results of the rapidly performed dU suppression test in human (SK-L7) leukemia cells, in methotrexate-sensitive and -resistant murine (L1210) leukemia cells, and in human tumor explants. The concentration of methotrexate resulting in a positive dU suppression test was closely correlated with the methotrexate concentrations required for growth inhibition in flask and soft agar culture systems. The fact that the dU suppression test can be rapidly interpreted in 4 hours compared to the longer period required for clonogenic assay suggests that further evaluation of this procedure as a rapid predictor for clinical antimetabolite response is warranted.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003114:Colony-Forming Units Assay; D004247:DNA / Q000096:biosynthesis; D003857:Deoxyuridine / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007939:Leukemia L1210; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D010051:Ovarian Neoplasms; D014410:Tumor Stem Cell Assay
D000964:Antimetabolites, Antineoplastic; D004247:DNA; D005472:Fluorouracil; D003857:Deoxyuridine; D008727:Methotrexate