Enhancement of fluoropyrimidine inhibition of cell growth by leucovorin and deoxynucleosides in a human squamous cell carcinoma cell line.
The growth inhibitory effects of the fluoropyrimidines 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) against a human squamous cell carcinoma cell line (SQ-1) were studied in the absence and presence of deoxynucleosides and/or N5-formyl-tetrahydrofolate (leucovorin). Inhibition of cell growth by the fluoropyrimidines was less when undialyzed rather than dialyzed fetal bovine serum was used. Leucovorin, in concentrations of 10(-6) to 10(-4) M potentiated the growth inhibition of FU and FdUrd; deoxyguanosine and deoxyinosine in concentrations of 10(-5) M also enhanced the growth inhibition produced by these fluoropyrimidines. In the presence of leucovorin addition, deoxyguanosine (10(-5) M) caused a further synergistic inhibition of cell growth produced by FdUrd but not FU. In contrast, addition of deoxyinosine at 10(-5) M resulted in further potentiation of FU but not FdUrd inhibition of cell growth in the presence of leucovorin. The synergy obtained with these combinations encourage the exploration of modulation of fluoropyrimidine by leucovorin and deoxynucleosides in vivo.
Chang
Y M
YM
Program Developmental Therapy, Memorial Sloan-Kettering Cancer Center, New York, New York.
Bertino
J R
JR
D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D003470:Culture Media; D003853:Deoxyribonucleosides / Q000494:pharmacology*; D004357:Drug Synergism; D005467:Floxuridine / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003470:Culture Media; D003853:Deoxyribonucleosides; D005467:Floxuridine; D002955:Leucovorin; D005472:Fluorouracil