Choline and
folate are interrelated methyl donors. Previous studies showed that
folate prevents genomic damage in human lymphocytes in vitro; however, the association between
choline and human
genomic stability is uncertain. To explore the genotoxicity, cytotoxicity, and
cytostatic effects and possible interactions of
choline and/or
folate deficiency on the human genome, lymphocytes from 6 volunteers were cultured in 18 combinations of
choline (CC) and
folic acid (FA) media for 9 days. The genotoxicity was evaluated by micronuclei, nucleoplasmic bridges, and nuclear buds in the binucleated cell; the cytotoxicity indices included apoptosis and
necrosis, and the
cytostatic effects were indicated by nuclear division index (NDI). Across all
choline concentrations, the frequencies of all
biomarkers except NDI were diminished when FA concentration was more than or equal to 120 nmol/L. The frequencies of micronuclei, buds, and
necrosis were significantly higher at lower levels of CC (0-6 μmol/L) compared with higher concentrations of CC (12-21.5 μmol/L) while maintaining the same FA concentration. We concluded that both
choline and
folate significantly impact
genomic stability and cell death, although effects of
folate were 2.5- to 6.2-fold greater, depending on the
biomarker and dose. A combination of 12 μmol/L CC and 120 nmol/L FA appears to be optimal for genomic integrity in vitro.