title: Induction of differentiation of HL-60 cells along the monocytic pathway by 5-methyltetrahydrofolate.
abstract: Many compounds of different chemical structure can induce the HL-60 cell line to differentiate along the monocytic or granulocytic pathway, but the mechanism(s) of differentiation by these agents is not known. Experimental evidence suggests that DNA and/or membrane phospholipid transmethylation reactions may be of importance. Based on this background, we have studied the effects of various concentrations of (dl)-5-methyltetrahydrofolate (mTHF), a folate coenzyme involved in transmethylation reactions, on differentiation of HL-60 cells. Differentiation along the monocytic pathway was evidenced in kinetic, functional, cytochemical and immunophenotypical studies when cells were treated with high-dose (dl)-mTHF (1 x 10(-3)M). Some hypotheses on the mechanism(s) of (dl)-mTHF induced HL-60 cell differentiation are discussed with particular regard to a possible enhancement of lipid or DNA methylation via methionine formation by the (l) form or to inhibition of folate-dependent metabolism by the unnatural (d) form, hence of purine and thymine nucleotide synthesis.
authors.affiliation: U.O. di Ematologia, U.S.L. 10/D, Firenze, Italy.
authors.forename: P A
authors.initials: PA
authors.lastname: Bernabei
authors.forename: E
authors.initials: E
authors.lastname: Mini
authors.forename: V
authors.initials: V
authors.lastname: Gattei
authors.forename: F C
authors.initials: FC
authors.lastname: Agostino
authors.forename: R
authors.initials: R
authors.lastname: Bezzini
authors.forename: R
authors.initials: R
authors.lastname: Saccardi
authors.forename: V
authors.initials: V
authors.lastname: Santini
authors.forename: M
authors.initials: M
authors.lastname: Coronnello
authors.forename: T
authors.initials: T
authors.lastname: Mazzei
authors.forename: P
authors.initials: P
authors.lastname: Rossi Ferrini
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D013763:Tetrahydrofolates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D006680:HLA Antigens; D013763:Tetrahydrofolates; C005984:5-methyltetrahydrofolate