Comparison of the conversion of 5-formyltetrahydrofolate and 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolates and tetrahydrofolates in human colon tumors.
Four hr infusions i.v. of [6RS]5-formyltetrahydrofolate ([6RS]5-CHO-H4PteGlu; 500 mg/m2) and [6RS]5-methyltetrahydrofolate ([6RS]5-CH3-H4PteGlu; 500 mg/m2) were compared for their relative effects on expansion of pools of 5,10-methylenetetrahydrofolates (CH2-H4PteGlun) and tetrahydrofolates (H4PteGlun) in two human colon adenocarcinoma xenografts in mice. Expansion of these pools by 253-661% of control and increase in predominance of di-, tri-, and tetra-glutamate species were observed during [6RS]5-CHO-H4PteGlu infusion. In contrast, only modest pool size expansion (148-164% of control) and limited modulation of polyglutamate species were detected in four tumor lines during infusion with [6RS]5-CH3-H4PteGlu. The data suggest that [6RS]5-CH3-H4PteGlu is less effective than [6RS]5-CHO-H4PteGlu as a precursor for pools of CH2-H4PteGlun and H4PteGlun in colon tumors.
Houghton
J A
JA
Department of Biochemical and Clinical Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38101.
Williams
L G
LG
de Graaf
S S
SS
Cheshire
P J
PJ
Wainer
I W
IW
Jadaud
P
P
Houghton
P J
PJ
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism*; D005260:Female; D005575:Formyltetrahydrofolates / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D011624:Pteroylpolyglutamic Acids / Q000096:biosynthesis / Q000302:isolation & purification; D013763:Tetrahydrofolates / Q000096:biosynthesis* / Q000378:metabolism*; D014183:Transplantation, Heterologous
D005575:Formyltetrahydrofolates; D011624:Pteroylpolyglutamic Acids; D013763:Tetrahydrofolates; C013123:5,10-methylenetetrahydrofolic acid; C005984:5-methyltetrahydrofolate