Researchers examine how oxygen radicals secure against cancer
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- Source: Goethe University Frankfurt
- Date: 26 Apr,2021
Initially, oxygen radicals – reactive oxygen species, or ROS for short – were thought of as exclusively harmful in the body.
They’re produced, by way of example, by smoking or UV radiation. Because of their high reactivity, they could damage many important molecules in cells, including the hereditary molecule DNA. As a result, there’s a danger of inflammatory reactions and the degeneration of affected cells to cancer cells.
Because of their damaging effect, however, ROS can also be intentionally produced by the body, for example by lung or immune epithelial cells, which destroy invading bacteria and viruses with ROS. This requires relatively high ROS concentrations.
In low concentrations, on the other hand, ROS play an important role as signalling molecules. For all these tasks, ROS are specifically produced by an entire group of enzymes. One representative of the group of enzymes is Nox4, which always produces small amounts of H2O2.
Nox4 is found in almost all body cells, where its product H2O2 maintains a large number of specialised signaling functions, contributing, for example, to the inhibition of inflammatory reactions.
Researchers in Goethe University Frankfurt, led by Professor Katrin Schröder, have discovered that by producing H2O2, Nox4 can even stop the progression of cancer. They examined mice that were unable to produce Nox4 because of a genetic modification.
When these mice were exposed to a carcinogenic environmental toxin (cancerogen), the likelihood that they would create a tumour doubled.
Molecular investigations showed that the H2O2 formed by Nox4 keeps a cascade going that prevents certain important signalling proteins (phosphatases) from entering the cell nucleus. If Nox4 and consequently H2O2 are absent, these signalling proteins migrate into the cell nucleus and as a consequence, severe DNA damage is barely recognised.
Severe DNA damage – e.g. double strand breaks – happens somewhere in the body every day. Cells react very sensitively to these DNA damage, setting a whole repertoire of repair enzymes in movement. If this doesn’t help, the cell activates its cell death programme – a preventative measure of the body . When such damage goes unrecognised, as happens in the absence of Nox4, it spurs cancer formation.
If Nox4 is missing and there is therefore no H2O2, the cells no longer recognise DNA damage. Mutations accumulate and damaged cells continue to multiply. If an environmental toxin is added that massively damages the DNA, the damage is no longer recognised and repaired.”
Katrin Schröder, Professor, Goethe University Frankfurt
The affected cells are not eliminated , but multiply, sometimes very quickly and invisibly, which eventually leads to the growth of tumours. A small amount of H2O2 thus maintains an inner balance in the cell that protects the cells from degeneration.”
Helfinger, V., et al. (2021) Genetic deletion of Nox4 enhances cancerogen-induced formation of solid tumors. PNAS. doi.org/10.1073/pnas.2020152118.