Reactive Oxygen Species

While some known carcinogens that promote colorectal cancer are diet and lifestyle related, others are not. Reactive oxygen species (ROS) is a collective term for highly reactive compounds that contain oxygen. ROS is ubiquitous and can be found throughout and produced by the body. However, this does not mean that our bodies are actively producing carcinogens. ROS can be found in our cells at low levels, and they serve important functions in cell signaling and homeostasis, or the maintenance of a stable inner environment.

They are, however, easily produced as a byproduct of oxygen metabolism, and escalated levels of ROS can become harmful to the body.

The ways in which ROS is produced is either endogenous or exogenous, that is, ROS can be produced within the body, or be introduced from an external source.

One of the ways in which ROS is produced is in the mitochondria of the cell. Mitochondria are important organelles that provide the cell with energy to function. Oxygen and glucose are required to produce that energy through a process known as cellular respiration, and ROS is produced as a byproduct.

At low levels, ROS is not overly problematic, but mitochondria-derived ROS can be increased as a result of exposure to radiation, inflammatory cytokines and other harmful factors. ROS may also be produced due to cellular responses to foreign substances, cytokines or bacterial infections, which can lead to escalated levels.

ROS does not enter the body as-is from the external environment. Instead, its precursors, which can be found in certain types of food, lifestyle vices like alcohol and tobacco, as well as environmental pollutants, are ingested and then metabolized to produce ROS.

In the colon, ROS production is mediated by the mucosal cells and innate immune cells. ROS generation during inflammatory conditions triggers signaling pathways that, with the help of commensal bacteria in the gut, help to resolve inflammation and maintain gut homeostasis. However, an overproduction of ROS can exacerbate inflammation instead of resolving it, and furthermore disrupt the gut microbiota that is important in the upkeep and protection of the epithelial lining.

In general, ROS promotes carcinogenesis by causing cellular and DNA damage along with inflammation through oxidative stress. ROS damages DNA by causing single strand breaks, and can destabilize the DNA strand when the nucleotide bases are oxidized. The base pairs commonly affected are the guanine-cytosine base pairs, which typically result in base-pair substitution mutations.

Managing endogenous ROS levels may not be possible, but reducing consumption of foods high in ROS precursors may be one way to manage ROS levels. Alternatively, consuming foods rich in antioxidants such as fruit and vegetables can help alleviate ROS damage.