Comparative effect of 6S, 6R and 6RS leucovorin on methotrexate rescue and on modulation of 5-fluorouracil.
The comparative efficacy of the pure diastereoisomers of leucovorin, the natural (6S) and the unnatural (6R) forms was compared to the racemic form (6RS). A protective effect in methotrexate-treated CCRF-CEM cells was obtained with 6S at concentrations 100-fold higher than those of methotrexate and with 6RS at concentrations 2-fold greater than those of 6S; however, at low concentrations of methotrexate, 6S was more effective than 6RS in preventing the cytotoxicity of methotrexate; on the opposite, 6R exhibited a protective effect at concentrations 10(4) higher than those of methotrexate. On the same cell line, 6S was shown to enhance the cytotoxic effect of 5 Fluorouracil exactly as 6RS while 6R did not exhibit any enhancing effect on cells exposed to 5 Fluorouracil.
Zittoun
J
J
Service Central d'Hématologie-Immunologie, Hôpital Henri Mondor Faculté de Médecine, Creteil, France.
Marquet
J
J
Pilorget
J J
JJ
Tonetti
C
C
De Gialluly
E
E
D000704:Analysis of Variance; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D003857:Deoxyuridine / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology*; D008727:Methotrexate / Q000494:pharmacology*; D013237:Stereoisomerism; D014410:Tumor Stem Cell Assay
D002955:Leucovorin; D005472:Fluorouracil; D003857:Deoxyuridine; D008727:Methotrexate