It is a fact of biology that cells need to divide. One of the defining features of a system to qualify it as being living is the ability to replicate and reproduce. When tissues in our body grow, more cells are being produced to make this happen. I’m sure that’s not a massive revelation to many of you. However, as our cells divide and form defined tissues, they know when to stop. They sense when they’ve divided enough to form a fully funtioning, say, liver or something. It’s a good enough system, which enables multicellular organisms to exist.
The cell cycle
In order to grow, cells have many specific genes in their genome which control and regulate growth. These genes can be switched on and off, like most other genes, and are controlled by various environmental and intracellular factors. Some genes, when switched on, will tell a cell to stop dividing. This is normal, and all part of a healthy system which gives our organs and tissues defined shapes and characteristics. The processes of cell division and growth are collectively known as the cell cycle, and errors in the cell cycle can lead to cancer.
Cancer is an uncontrolled prolifieration of cells, where cells no longer have restrictions on their growth. They divide pretty much indefinitely. It is this growth which leads to tumour formation. Tumours are the end product of the release of inhibition of the cell cycle. Tumours are commonly divided into two types, benign and malignant.
- Benign tumours are considered to be the ‘safe’ tumours, which aren’t life threatening. Benign tumours can grow indefinitely, but stay at their site of origin - they don’t spread around the body and seed tumours to grow elsewhere. Benign tumours are usually a uniform cell type.
- Malignant tumours can be deadly. Malignant tumours also grow indefinitely, but can spread to other parts of the body (making them dangerous). The process of a tumour invading other parts of the body is known as metastasis. Malignant tumours can be full of different cell types as malignant tumour cells are capable of differentiation. The differentiation of cells is known as anaplasia.
It is important to note that cancer is not a ‘modern’ disease. We certainly notice it more now, and it certainly does have an increased prevalence now due to certain factors of our life style which I shall probe shortly - but it has been around for longer than there have been humans. Fossil evidence has shown dinosaurs with bone tumours. Or more recently in the geological time scale, ancient greek physician Hippocrates performed mastectomies on women with breast cancer.
Cancer is a slow process. Tumours grow slowly. They certainly grow at a slower rate than most other tissues in the body. When somebody finds out they’ve got cancer, even if you say you’ve ‘caught it in the early stages’, that cancer has probably been hanging around for quite some time (and I don’t just mean a few weeks, either). It’s just not noticeable to begin with.
Cells become cancerous when genes involved in regulating the cell cycle become mutated or damaged. Genes which control growth are called oncogenes. Onco- from the greek for ‘lump’. Study of cancer is ‘Oncology’ etc. Oncogenes (much like every other gene) can be damaged by certain viruses, UV light (from the sun - which is why sunbathing without skin cream greatly increases cancer risk), by various carcinogen chemicals such as benzene or benzoapyrene (these, amongst others, are flat planar molecules which cause DNA to be misread during replication, causing mutations to be formed), and high energy ionising radiation, such as that from entering a radioactive zone. Other genes whose damage is also involved in initiating cancer are tumour suppressor genes, whose role it is to ordinarily halt growth of a cell.
A carcinogen is a substance which induces high-risk mutations in a cell, and as such can also be referred to as a mutagen. However, another way cancer can be initiated is via mutations in genes responsible for programmed cell death (apoptosis). Ultimately, cancer is an imbalance between processes controlling cell death and cell growth. Programmed cell death exists for a few reasons, but in this context it is there to remove any extra cells that just aren’t needed anymore. If the processes which control cell death are disrupted on a wide scale, then extra cells will continue to persist and tumours will gradually form.
In fact, mutations don’t really need a mutagen to induce them. In order for a cell to divide, it needs to create a copy of it’s DNA so both subsequent cells have a genome. DNA replication is a relatively efficient process, and usually does the job. The protein machinery which replicates DNA isn’t 100% efficient and does make mistakes from time to time.
A single mutation cannot turn a cell cancerous, but rather an accumulation of mutations does. A minimum of 6 mutations, in different genes would be roughly the minimal amount of damage to turn a cell a cancerous. The probability for 6 of the right kind of mutations to occur in the right genes in a single cell cycle (a single cell division) is about 1 in 1,000,000,000,000,000,000,000,000,000,000,000,000,000,000. Of course, what could happen is a cell that divides a lot has a single mutation, passes it on to its progeny, and over a few generations it amasses enough mutations. The chances of this are much higher. To this point, the most commonly occurring cancers occur in tissues with a high cell turnover rate. For this reason, guys should keep regular checks on their testicles, as loads of sperm are produced there everyday.
All in all, the overall chance of a cell becoming cancerous naturally is still about 1 in 100,000,000,000,000. And even by that point, a single cell turning cancerous won’t necessarily translate into full blow tumour formation. The body can recognise cancerous cells to a certain degree, and deal with them. Tumour formation is usually permitted by later stage immunocompromise and other factors. Of course, cancer is much more prevalent than these numbers would have us believe. That is because environmental (and other cellular) factors haven’t been considered. The natural background radiation from our cosmic environment (the sun and the universe!), pollution, the food we eat, volcanoes, industrial radiation and even our very own metabolism come in and increase the probability of mutations. Smoking and ionising radiation massively, massively increase the risk. Smoking releases high energy molecules and mutagens into the body, wreaking havoc with DNA. Ionising radiation physically interferes with the DNA itself, potentially changing the chemical composition of the base pairs that make up DNA. What the newspapers should be saying when they say ‘-gives you cancer’ is ‘raises your risk of developing cancer’ (here’s looking at you, Daily Mail, or Daily Fail as I like to call it)
Our own mitochondria release high energy molecules called free radicals which can interfere with DNA in similar ways to ionising radiation. Indeed, organisms with a high metabolism (who therefore have more mitochondria per cell), such as mice and small birds, have shorter lives because the higher concentration of mitochondria inflict more damage on their DNA (this doesn’t necessarily mean they all die of cancer, but it could lead to it - though they may have evolved systems to combat the cancer risk to compensate - I would imagine). This free radical damage is majorly implicated in contributing to the ageing process. Mitochondria are absolutely crucial to all multicellular life on Earth, as they are our power generators. But it’s also an evolutionary compromise to have them, as they’re liable to releasing harmful chemical species. Organisms do have systems in place to deal with radicals, and scientists have tried to utilise these to increase our health. Antioxidants anyone? They sequester radicals, and prevent harmful oxidation of DNA and proteins which contribute to ageing, and possibly cancer. It’s but one reason why vitamin C and vitamin E are so important.
Mitochondria in free radical production
Cancer cells can be deadly, but are fascinating none the less. They behave completely differently to normal healthy cells, almost as if they have a mind of their own. They manipulate the body to make it ideal for them to survive, they have systems in place to enhance their own survival, avoid the immune system and to help them invade other tissues (something I’ll explore at a later point). They become rogue cells. Considering the factors, in reality, one can simply get cancer from sitting around trying to avoid the big world. The very processes that keep us alive can kill us through their own inefficiencies - though this chance is much smaller, than from say a smoker, a liquidator at Chernobyl, or someone who loves sunbeds or something.