Vitamin D has protective effects against cyclophosphamide-induced genomic instability in CHL cells in vitro and in mice in vivo

抄録

Vitamin D is required in organisms ranging from single cells to plants and animals, including humans, and adequate vitamin D is crucial for health. Some autoimmune diseases and cancer can develop due to genomic damage and epidemiological studies have revealed the possibility that vitamin D has effects on genomic stability. We investigated the effects of vitamin D on genomic instability induced by cyclophosphamide (CP) in CHL and bone marrow cells (BMC). The effects of 1α,25-(OH)₂D₃ and vitamin D₃ were tested by analyzing chromosomal aberrations (CA) in vitro and micronucleus formation (MN) in vivo, respectively. The extent of DNA damage was determined by alkaline comet assay and immunofluorescence of phosphorylated histone H2AX. 1α,25-(OH)₂D₃ at 10, 50 and 100 nM reduced CA, with a protection ratio of 40.7–44.0%. Two injections of vitamin D₃ of 1000, 5000 and 10000 IU spaced at an interval of 1 week had a suppressive effect on MN, with a protection ratio of 36.7–44.5%. Vitamin D mitigated DNA damage, especially in terms of a dose-dependent decrease in double-stranded breaks (DSBs). Our data suggest that vitamin D has protective effects on genomic stability by diminishing CA and MN, which can mainly be attributed to mitigation of DNA damage, specifically via a dose-dependent decrease in DSB. In summary, vitamin D showed protective effects against CP-induced genomic instability by diminishing CA in CHL cells in vitro and the MNPCE frequency in mouse BMCs in vivo. These effects can mainly be attributed to mitigation of DNA damage.