Free Radicals, Cancer, and Oxidation: The Rusting of our Body

Growing up in Pittsburgh, I am no stranger to steel. In a city strewn with steel bridges and steel mills, we are no strangers to rust (especially with the Steelers in the past several years). Driving across the Roberto Clemente Bridge to the North Side and Heinz Field or the David McCullough Bridge to the Strip District, a simple glance upwards always reveals some rust breaking through the yellow paint-coated steel beams.

The Roberto Clemente Bridge replaced the original massive innovative bridge created by John Roebling. Roebling, who designed the Brooklyn Bridge, lived just outside of Pittsburgh in a German settlement called Saxonburg. He and his family had left Prussia for Pittsburgh, thanks to a lack of jobs resulting from the Napoleonic wars.

Roebling spent most of his career fighting rust. Steel was favored as a primary metal used in bridge design for its strength, permanence, and malleability, which allowed it to be molded to design projects. Furthermore, with a fresh coating of paint, a steel bridge can look brand new. When Roebling made his first bridge, he had to plan on combating gravity, wagon and train weight, wear and tear, and the rust that would form on the surface of the steel. He combined ingenuity with his unmatched design intellect for the former, but combating the latter was nearly impossible.

The beams and wires supporting the bridge were made from steel, the supple metal mixture created by blasting pig iron with carbon. The subsequent metal was cheap and strong, but slightly flexible – a natural pick for structural design. The downside, however, is that the iron in steel eventually forms rust from its exposure to oxygen. The reddish/brown material known as rust is iron oxide, or in other words, the flaky metal that forms when iron interacts with oxygen and water or moisture during the process known as oxidation. This combination of large steel structures resting in water creates a recipe for rust that is and was nearly impossible to avoid. During oxidation, the formation of acidic compounds begins to degrade the iron, and over enough time, the entire structure can corrode and turn to rust.

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The David McCullough Bridge, honoring the Pulitzer Prize winning author from Pittsburgh.

Roebling’s third and final bridge in Pittsburgh was eventually replaced by a temporary bridge and then the Roberto Clemente Bridge, which still stands today. They floated the replacement down the Ohio River, and ultimately used it in the construction of the Coraopolis bridge, which, 100 years later, allowed me easy access to the Neville Island Roller Rink during my grade school roller skating parties.

Oxidation and rust in our cells

During all those trips across the bridge, staring at the rust forming on it, I never once contemplated that the same process was occurring in my body. Just as Roebling’s steel bridges were constantly being bombarded with water and oxygen to produce rust through the process of oxidation, so were my cells. When iron is exposed to oxygen, those oxygen molecules eventually pull away electrons, the negatively charged particles rotating around atoms. The loss of electrons produces hydroxide, which causes corrosion, rust, and ultimately, destruction of the steel.

Many rusty bridges like this jut across the rivers in Pittsburgh.

Much like the importance of steel in bridge design and construction, our cells rely on the process of oxidative phosphorylation, which, in the presence of oxygen breaks down our nutrients to derive energy. A highly efficient method of energy derivation, the process does not come without glitches. It takes place in the microscopic cells of our body – which are composed of 60% water – in the presence of oxygen. Additionally, electrons are passed around during the process, creating a recipe that, much like Roebling’s bridges, are apt to get a little rusty.

The tiny details of the process are less important, however, it is important to note that oxidation occurs, and there is not much we can do to stop it. Atoms dislike it when they gain or lose electrons, as it makes them unstable, forming radicals – the highly reactive molecules with one or more unpaired electrons in their outer orbit. (In the oncology world, we use this to our advantage as we bombard cancer cells with free radicals in hopes that the damage is fatal.) Unlike with Roebling’s bridges, no rust occurs in this instance, and instead, the pulling of electrons and reaction with oxygen from the process creates free radicals and byproducts like superoxide, hydrogen peroxide, and hydroxyl. Instead of creating the damaged steel that is all too commonly seen throughout Pittsburgh, these reactive substances damage our cells and tissue through corrosion, leading to aging and cancer from DNA damage. The double-edged sword, much like the inescapable need for steel’s strength and flexibility in bridge design, is the absolute requirement of oxygen and oxidative phosphorylation by our cells to produce vital energy. The tradeoff, however, produces free radicals that age our cells and eventually lead to our demise.

Hydrogen peroxide, which is not a free radical, is formed within our cells during the production of energy. While this substance may be harmless, in the presence of an oxygen radical and an iron compound, a reactive hydroxyl radical is formed. If this process sounds familiar, it should – our cells our beginning to rust. Perhaps most concerning is the ability of these free radicals to bind and damage polyunsaturated fatty acids located around our cells. The free radicals bind to the fats, stealing electrons, damaging their structure, and resulting in a process called lipid peroxidation where the free radical parks itself in the fat. You may have experienced this first hand if you left vegetable oil cooking on a pan for too long and watched as it eventually begins to smoke, and much like an unprotected steel bridge, turns brown and oxidized. The free radicals can also act like grenades, blowing holes in the protective fatty membranes of our cells.

The Good News

While free radical damage, also known as oxidative damage, produced from our own cellular processes is an unfortunate type of self-destruction, these free radicals can also be used to kill infections. They also act as messengers and important components of cellular signaling.

However, several external sources of free radicals can cause similar oxidative damage. Free radicals can damage all aspects of our body and cells, attacking our proteins and fatty cellular components. Free radicals attack LDL cholesterol along the walls of our arteries, leading to atherosclerosis.1 By far, the worst type of injury is oxidative damage to our DNA. Damage to the pairs of nucleotides within DNA or, worse yet, breaks between the strands of DNA lead to errors when that DNA is read for protein construction.2 The damage can also inactivate certain parts of DNA while prompting others. Deactivating a gene that signals for cells to stop replicating could lead to unchecked cellular reproduction and cancer.

Newer steel production techniques have figured out how to combat rusting. Painting the steel to limit the exposure of water and oxygen, or coating it with chromium to produce stainless steel can minimize oxidation and rust. An older and cheaper technique, known as galvanization, electroplated the surface with zinc. If you have ever watched brown water pour out of a faucet, you are familiar with the issues of galvanized steel pipes. Finally, rubbing oil or other chemicals on the steel can provide a small amount of protection, as can running an electric current through it or using rust inhibitors (which are generally ineffective).

Lucky for us, our cells have adapted to the barrage of free radicals produced during energy derivation over the past several million years. They have developed the antioxidant defense system that activates certain enzymes, like catalase, superoxide dismutase, and peroxidases, to produce antioxidants to neutralize the free radicals. The process is so vital for life that inactivating it in mice can be rapidly fatal. This system senses free radical levels and produces antioxidants to counter them. Some evidence suggests that based on the type and amount of free radical production, our cells may produce a larger than necessary amount of antioxidants to detoxify the free radicals and halt oxidative damage.3,4 Furthermore, much like the protective layer of yellow paint covering the bridges of Pittsburgh, fat-soluble antioxidants like vitamin E are located along the fatty membranes that surround cells to provide protection directly where free radicals attack.

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However, much like the rusting of steel, free radical damage is guaranteed to plague us as long as we are breathing. Furthermore, like the failed attempts to stop rusting through galvanization, oil coatings and rust inhibitors, antioxidant supplements have failed to help in this battle and, much like the brown liquid pouring out of a galvanized faucet, may actually worsen issues and increase the risk of death in those who use them.5,6 Paralleling the need to continually repaint the golden bridges jutting across the three rivers in Pittsburgh (there are 446 bridges in total), a little effort can go a long way to stop the rusting of steel and the accumulation of free radicals in our cells. Adequately stressing them acute stressexercise, cruciferous and allium vegetables, sprouts, fasting and carbohydrate restriction, spices, and maybe even a little red wine upregulates our antioxidant defense system to fight free radical damage before it starts. Stressing our cells signals for them to continually paint that protective yellow barrier to limit oxidative damage and avoid rusting.

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Oxidation References:

  1. Spiteller, G. The relation of lipid peroxidation processes with atherogenesis: a new theory on atherogenesis. Mol. Nutr. Food Res. 49, 999–1013 (2005).
  2. Schulz, T. J. et al. Induction of Oxidative Metabolism by Mitochondrial Frataxin Inhibits Cancer Growth: Otto Warburg Revisited. J. Biol. Chem. 281, 977–981 (2006).
  3. Schulz, T. J. et al. Activation of mitochondrial energy metabolism protects against cardiac failure. Aging (Albany. NY). 2, 843–853 (2010).
  4. Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G. & Gluud, C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297, 842–57 (2007).
  5. Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G. & Gluud, C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane database Syst. Rev. 3, CD007176 (2012).

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