Life of a Cancer Cell

Cancer, a word that has more than 700 million hits on Google, that features in 100 million news articles and affects, directly or indirectly, the majority of the world population, still remains a mystery to us.

So, what is cancer and where does it come from?

We have trillions of cells in our body and cancer comes from a single one of those cells. Every day, each cell in our body is exposed to agents that cause damage to the DNA. These agents can be external, such as UV light while sitting in the sun, radiations from an x-ray scan, alcohol consumption (1) [1], smoking (2), pollutants (3) [2], burnt food [3], food chemicals (4) [4] and many more, all acting as attackers to the DNA; on top of these, internal agents, like oxygen free radicals, are also damaging to the DNA. The truth is that, if we sat in a dark room, drinking nothing but water, and breathing only clean air, our cells living their daily life (and carrying out essential cellular processes) still get damaged in their DNA. Indeed, every day, each individual cell suffers up to a million lesions to the DNA. Multiplied by every cell in our body, that’s a huge amount of damage to be repaired!

 

A flower of cells

Confocal microscopy image of human osteosarcoma cancer cells that show damage to their DNA (green and red dots). DNA stained in Blue.
Image by Simona Giunta

However, fear not, our body is perfectly equipped to handle it! We’re able to repair the damaged DNA and have proteins in our cells designed to efficiently detect and identify basically every type of DNA damage within seconds from their occurrence; these proteins work hard 24/7 to repair the damaged DNA and maintain the cell open and operative for its usual cellular business!

You can imagine, though, that there might be times when the damage covers a very large area of DNA and it’s too extensive to be repaired. Even in this situation, the cell is smart and is able to assess when it’s too badly affected and knows when it would be impossible to repair such large damage. In this case, the cell makes the executive decision to commit suicide. Cells in the body work as an altruistic society, where all aim to contribute to the greater good of the body in a selfless way. The health of the whole body is more important than the life of an individual cell, especially if damaged. Thus, the cell that is too badly damaged and basically unable to function, or to function properly, will activate a ‘programmed cell death’ process, called apoptosis.

‘Apoptosis’ is a word that derives from Greek, meaning ‘falling away’. Like leaves from the tree, apoptotic cells ‘fall away’ from our body. A good example of apoptosis due to DNA damage is our skin peeling after sun burnt, representing thousands of cells literally falling off our body.

The destiny of a damaged cell that can no longer act in a positive manner toward the health of the whole organism is cell death, removing itself to avoid being potentially deleterious to the entire system.

The cancer cell, on the other hand, is a selfish cell that doesn’t want to die! It’s a badly damaged cell that, childishly, throws a tantrum, moaning “I don’t want to die! I don’t care I am damaged, I am staying put, I’m not going anywhere!”. The cancer cell is individualistic and does not face up to the reality of its situation of being too damaged to function. In fact, the cancer cell doesn’t care it can no longer contribute to the good of the body, it merely thinks of itself and its own survival. Obviously, that is a short-sighted view on the cancer cell side, as the survival of a single – badly damaged – cell can become dangerous and possibly lead to the death of the body! Our body, though, is also equipped to act against these ‘selfish’ cells that do not die, mounting an immune response against them and getting rid of them.

Although the anthropomorphization of the cancer cell as a selfish cell is suited, even from a biological stand point, the scientific truth behind the cancer cell is that the cell knows it should die, would actually like to die, but the cancer cell cannot die! What happens is that this cell is damaged right in the point of the DNA that it needs to read to be able to know how to die and activate the cell death pathway! It would like to die, but doesn’t know how to! This is, somewhat, a rare event as we have 6 billion pieces of code in our DNA, the so-called DNA letters (A T C G, respectively: adenine, thymine, cytosine and guanine) and the fact that an unrepairable damage falls right in the point that the cell needs to access to know how to die it’s extremely unlucky! Of course, as we live longer lives, perhaps beyond our own evolutionary age, in this increasingly polluted Earth, drinking alcohol, smoking and eating processed, semi-synthetic, chemicals filled food, exposed to dangerous toxins, you can see how, day after day, cells get increasingly damaged. Been damaged over and over, the probability that a cell in the body loses control over it’s own ability to die, to divide, to live life in a calm, paced manner and instead starts speeding through life – as some of us also do – is not so unlikely after all!

And this could be the reason why cancer incidence increases hugely with age and the way we live also has a clear role in this. Several scientific evidence show that about 60% of cancers are what scientists call ‘sporadic’ cancers [5], which have not been found to be directly influenced by our genes and genetic make-up, but can be considered life-style induced. The remaining ~ 40% are the ‘hereditary’, ‘familiar’ and genetic cancers, often childhood cancers belong to this category, where the body has inherited a mutation from the parents that does not allow cells to function properly or that makes them defective in repairing DNA damage correctly – as for Angelina Jolie with an inherited BRCA1 mutation [10], hence, making the person more susceptible to cancer and at risk of developing cancer at a much earlier age.

As a cancer researcher, I get asked almost on a daily basis this question: do we have a cure for cancer yet?

And, inherited cancers aside, the best cure for cancer, honestly, is prevention!

If you think that lung cancer is the most common cause of cancer-related death worldwide [6] and that 4 in 5 lung cancer are caused by smoking [7], just by stopping smoking, we could reduce those 4/5 of lung cancers, 1 million death each year, and almost one fourth of all cancer death across the globe! [8]

Because cancer is not just one but hundreds of heterogeneous diseases, where each needs it’s own medical treatment and management, prevention is extremely important, across the spectrum of all cancers, more than any cure from any Nobel Prize winner biologist (although those cures become essential once cancer is already present)! Because the very first steps in a cancer cell’s life is the DNA damage leading to a mutation, and this very first event in carcinogenesis is common in all types of cancers, minimizing DNA damage through prevention is the best action in fighting cancer.

Minimizing damage to our DNA is the best thing we can do to fight cancer

Sure, changing our lives, living better, eating better (for starter, at least 400 gr of fresh vegetables and fruit a day, as from WHO recommended guidelines [9]), avoiding harmful chemicals, quitting smoking, demanding clean air and water, exercising, all of these activities combined are by no means a guarantee of a cancer-free life. During our long lives, it might still happen. However, I like to put it down to the ‘crossing the road’ theory of probability:

When you are crossing a road, it is highly recommended that you look before crossing. Nonetheless, it is not actually 100% guaranteed that looking will save your life. You might look carefully before crossing, then, in a moment of bad luck, a car comes from around the corner at fast speed and hits you! On the other hand, you could decide to cross the road without watching and you could be lucky to do it when no one is coming and never get hit (unlikely in New York and any other city in the world, so don’t do it!). Sure, it’s unluckily and that’s the same for cancer. If you live carelessly, you might always be lucky and never get hit. Vice versa, you could lead a healthy life, yet still get cancer. But as a general rule, if you live well, you decrease your chances to have cancer (and many other diseases!) enormously and if you live badly, well… who would be so crazy to cross a road without looking anyway!!!

The Beatles crossing Abbey road without looking!

The Beatles were not looking for incoming traffic and were lucky not being hit crossing Abbey Road! Similarly, millions of people in the world live “without looking”, posing themselves at an increased cancer risk. Don’t be reckless, no crossing/living without looking!

The secret is right in our hands. We could be lazy about it, maintaining the status quo and just waiting in the hope that scientists come up with a magic pill after years of of lab work and more years for clinical trials, drug approval and commercialization, and then pay thousands of dollars for the entire treatment or… we could act now to change not only our life, but also our planet for the better, for good!

On this note, I urge every single soul on this planet to look before crossing the road, to wake up tomorrow and take ownership of their lives and their world, and to make a change for the better, for the greater good of this amazing thing we live in – our body!

 

Dr. Simona Giunta, Ph.D. and Cancer Researcher.

REFERENCES & SOURCES:

1.         N. Kotova et al., Carcinogenesis 34, 325 (Feb, 2013).

2.         C. S. Kao-Shan et al., Cancer Res 47, 6278 (Dec 1, 1987).

3.         R. Andreoli et al., Med Lav 103, 324 (Sep-Oct, 2013).

4.         Y. F. Sasaki et al., Mutat Res 519, 103 (Aug 26, 2002).

 

FOOTNOTES, ADDITIONAL READINGS & ORIGINAL ARTICLES:

[1] ” […] we demonstrate that an intake of 10% alcohol for 4 weeks in rats is genotoxic due to induction of micronuclei. Acetaldehyde (AA), the first product of ethanol metabolism, is believed to be responsible for DNA damage induced by alcohol.”

[2] Biomarkers of exposure to benzene increased as a function of environmental air pollution and urbanization level; (ii) U-Benz clearly distinguished both exposure to ETS and areas of residence, whereas benzene metabolites were associated only with the latter; (iii) the variance of 8-oxodGuo and 8-oxoGuo was accounted for by environmental benzene exposure, thus suggesting that benzene is a good tracer of other components of complex mixtures of pollutants causing oxidative damage to nucleic acids.

[3] One solid reason to not eat burnt food is that it contains polycyclic aromatic hydrocarbons (PAHs), which are a class of air pollutants. Some of these chemicals have been proven to be carcinogenic, and some are even found in coal tar and cigarette smoke. The toxicity of PAHs depends heavily on its structure; while many PAHs may have the same chemical formula and same number of rings, different isomers can vary from being nontoxic to being extremely toxic.

The most well-known of PAHs is benzo(a)pyrene, which damages DNA, which in turn can possibly cause cancer. Cooked meat products contain up to 4 ng/g of benzo(a)pyrenes and up to 5.5 ng/g in fried chicken. However, in overcooked beef, the amount of benzo(a)pyrene can reach over 60 ng/g.

[4] ” We determined the genotoxicity of 39 chemicals currently in use as food additives. They fell into six categories-dyes, color fixatives andpreservatives, preservatives, antioxidants, fungicides, and sweeteners. We tested groups of four male ddY mice once orally with each additive at up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow 3 and 24h after treatment. Of all the additives, dyes were the most genotoxic. Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal induced dose-related DNA damage in the glandular stomach, colon, and/or urinary bladder. All seven dyes induced DNA damage in the gastrointestinal organs at a low dose (10 or 100mg/kg). Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced DNA damage in the colon at close to the acceptable daily intakes (ADIs). Two antioxidants (butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)), three fungicides (biphenyl, sodium o-phenylphenol, and thiabendazole), and four sweeteners (sodium cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA damage in gastrointestinal organs. Based on these results, we believe that more extensive assessment of food additives in current use is warranted.”

[5] Sporadic cancers – these are cancers that occur by chance in individuals who have no known genetic risk factors and no significant family history. Approximately 60% of cancers are sporadic.

[6] Wiki: Worldwide, lung cancer is the most common cause of cancer-related death in men and women, and is responsible for 1.38 million deaths annually, as of 2008.[11]

[7] SMOKING IS THE SINGLE BIGGEST CAUSE OF CANCER IN THE WORLD. ” Experts agree that smoking is the single biggest cause of cancer in the world. Smoking causes over a quarter of cancer deaths in developed countries and nearly one in five cancer cases. Around half of current smokers will be killed by their habit if they continue to smoke. And 25-40% of smokers will die in middle age. Smoking causes even more deaths from other respiratory diseases and heart conditions than from cancer. If current trends continue, scientists estimate that tobacco will kill about one billion people in the twenty-first century. Smoking greatly increases the risk of lung cancer. A 2011 study found that more than four in five lung cancers are caused by smoking. In 2002, lung cancer killed around 33,600 people – about one person every 15 minutes. Tobacco smoke was first shown to cause lung cancer in 1950. This study found that people who smoked 15-24 cigarettes a day had 26 times the lung cancer risk of non-smokers. And people who smoked less than 15 cigarettes a day still had 8 times the lung cancer risk of non-smokers.”

http://www.cancerresearchuk.org/cancer-info/healthyliving/smokingandtobacco/howdoweknow/tobacco-smoking-and-cancer-the-evidence

[8] http://www.cancerresearchuk.org/cancer-info/cancerstats/world/the-global-picture/cancer-overall-world

[9] http://www.who.int/dietphysicalactivity/fruit/en/index2.html

[10] http://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html

 

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