Epigenetic regulation of colorectal cancer by immune cell oxidants and gut bacteria

Mutations in DNA cause cancer, but cancer can also occur through changes to chemical signatures on DNA (such as methylation) without altering the genetic code itself. We recently discovered that certain oxidants released by activated immune cells directly alter DNA methylation patterns in cells. These oxidants, called chloramines, are produced through the reaction of HOCl (chlorine bleach) and nitrogen containing compounds called amines. Rates of colorectal cancer (CRC) are very high in NZ and its development and progression is strongly associated with gut inflammation. Mounting evidence also suggest that gut resident bacteria have a role to play in CRC progression. The CRC microenvironment represents a setting where a reaction between HOCl produced by stimulated immune cells and amines produced by gut bacteria is likely to occur. We would now like to examine how chloramines influence DNA methylation in CRC cells. Furthermore, we will determine if other compounds produced by gut bacteria enhance production of the oxidants in immune cells. This research will provide new insight into how the microbes in our gut combine with immune cells to promote CRC. This may lead to new strategies for preventing or slowing the progression of this devastating disease.