Tetrahydrofolic acid

Tetrahydrofolic acid (L-5,6,7,8-Tetrahydrofolic acid) is the biologically active vitamin B9 folate derivative. Tetrahydrofolic acid is a donor of one-carbon groups for amino acids, nucleic acids, and lipids. Tetrahydrofolic acid serves as an acceptor of free formaldehyde, producing 5,10-methylenetetrahydrofolate-Tetrahydrofolic acid^[1]. In Vitro:Tetrahydrofolic acid (0-200 μM; 3 days; Adh5^-/- DT40 cells) exposure is cytotoxic to Adh5- and Fanconi anemia (FA)-deficient cells due to the accumulation of extensive DNA damage and chromosome breaks^[1].
Tetrahydrofolic acid (0-100 μM; 16 hours; Adh5^-/- DT40 cells) treatment strongly promots FANCD2 and ser139-H2AX focus formation in Adh5^-/- cells in a dose-dependent manner^[1].
Tetrahydrofolic acid exposure activates the DNA damage response (DDR) due to uncontrolled activity of the thymidylate synthase enzyme, which causes a depletion of essential nucleotides, and promotes repair by a homologous recombination mechanism^[1]. In Vivo:Tetrahydrofolic acid (62.5 mg/kg; intraperitoneal injection; daily; Adh5^-/- mice) treatment perturbs the hematopoiesis of hematopoietic cells, increases ser139-H2AX phosphorylation, and decreases the survival of progenitor cells (HSPCs) suggesting that excess Tetrahydrofolic acid could be mutagenic and genotoxic to bone marrow cells^[1].