Pteroylglutamic (folic) acid fails to protect HL60 cells against cyanocobalamin [c-lactam]. “PGA-Hcy” medium was RPMI 1640 without methionine and without folic acid, containing L-homocysteine thiolactone at 200 μmol/L, pteroylglutamic acid at 200 nmol/L, vitamin B₁₂ at 3.7 nmol/L, and dialyzed serum. Cyanocobalamin [c-lactam] at 7.4 μmol/L caused growth arrest followed by cell death, and this effect was reversed by additional concentrations of vitamin B₁₂ (7.4 μmol/L). High concentrations of pteroylglutamic acid (up to 20 μmol/L) did not reverse the cytotoxicity (data not shown). Pteroylglutamic acid, a nonmethylated folate, fails to prevent the cell death caused by cyanocobalamin [c-lactam]. Methyl group trapping is, therefore, not the cause of the cytotoxic effect of the inhibitor. •, “PGA-Hcy” medium alone; ○, “PGA-Hcy” plus c-lactam; ▪, “PGA-Hcy” plus additional vitamin B₁₂ ; □, “PGA-Hcy” plus c-lactam and additional vitamin B₁₂ .