Smoking is clearly bad for you. If bad breath, hacking coughs and emphysema aren’t bad enough, there is always lung cancer to ruin your day. Although there’s tons of evidence linking smoking to aberrant DNA methylation and lung cancer, researchers still haven’t figured out what exactly kicks off that whole process.
Some talented scientists from City of Hope in Duarte, CA set out to investigate how smoking-related carcinogenesis begins by focusing on one main suspect, the smoke-derived carcinogen benzo[a]pyrene diol epoxide (B[a]PDE). The team exposed normal cells to B[a]PDE and then used their Methylated CpG Island Recovery Assay (MIRA) paired up with microarrays to check for any DNA methylation changes within cancer related regions. Surprisingly, what they found was that the B[a]PDE treated cells had nearly identical global methylation patterns to untreated cells. Clearly B[a]PDE isn’t the carcinogenic trigger they were looking for.
So does this mean the whole connection between smoking, DNA methylation and lung cancer has all gone up in smoke? Well, not exactly…the authors point out a few possible explanations for their results:
- B[a]PDE is just one of many carcinogens found in smoke. Perhaps other compounds, or sets of compounds, can trigger aberrant DNA methylation.
- The relatively short study timeframe means that they weren’t able to rule out aberrant methylation as a rare, single cell event that might show up later through a growth advantage.
- Carcinogens may have other epigenetic effects, like histone modifications, chromatin remodeling or miRNA regulation, that then go on to alter DNA methylation secondarily.
Even though the group from City of Hope didn’t show that B[a]PDE exposure triggers aberrant DNA methylation leading to lung cancer, they were able to prove that their MIRA-assisted microarray method works well for looking at the initiating events in cancers.
Get all of the smoke-free facts in PLoS One, May 2010.