Radiation therapy usually works well against cancer, but some cells that survive the blast can divide and become unstable (cancerous) much later on, causing a relapse. Researchers initially thought that DNA hypomethylation was to blame for “delayed radiation-induced genomic instability,” but a new study in Epigenetics, August 2012 shows that, at least for embryonic stem cells, this isn’t the case. Though DNA methyltransferases (DNMTs) probably are involved. Yeah, it’s complicated.
Some cells that initially survive radiation are kind of like stem cells (they are even called “cancer stem cells”), so a U.K. team tested five different mouse embryonic stem cell lines and compared them before and after a biologically-relevant radiation dose. One cell line was the wild-type; the other four had mutations in DNMTs and had hypomethylated DNA. Here’s what they found:
- Global DNA methylation levels didn’t change in any of the cell lines after irradiation, and methylation didn’t have anything to do with survival or radiation sensitivity. (But DNMT3s may make cells slightly resistant to radiation.)
- The researchers didn’t see differences in the cell lines with regard to DNA damage, oxidative stress, or chromosomal instability after irradiation.
- Global methylation had no effect on the mutation rate at a single gene (Hprt) locus. However, Dnmt1-/- cells had lots of mutations there.
- Wild-type cells showed delayed radiation-induced genomic instability, but none of the mutants did.
The group says that the results show that even though global DNA methylation levels aren’t associated with a delayed radiation response in embryonic stem cells, DNMTs are necessary.
Don’t delay! Read the details at Epigenetics, August 2012.