Friday, July 18, 2008

Stars, radiation, DNA, and cancer

There are in the order of 100 billion (1011) stars in a typical spiral galaxy, such as our own Milky Way. Only about a thousand of these are visible to the naked eye at any one time, in the absence of light pollution. In contrast, there are in the order of 100 trillion cells (1014) cells in the human body. That's a thousand cells for every star in the Milky Way.

Within almost all of those 100 trillion cells is a nucleus which contains DNA. The DNA suffers various types of damage on a routine basis, and in fact, an estimated 2,000,000,000,000,000,000 DNA lesions occur per person, per day! Whilst there are copious DNA repair mechanisms within each cell to deal with this damage, they aren't 100% effective.

The most serious types of lesion are double-strand breaks. DNA is, famously, a double-helix, and when both helical strands are ripped asunder, this is referred to as a double-strand break. Double-strand breaks are capable of causing DNA mutation, and certain types of DNA mutation lead to the formation of cancer.

Whilst some of the DNA damage is caused by chemicals, radiation is also capable of causing DNA damage. Everyone on the Earth is subject to a background level of radiation, which averages about 2.4 milliSievert per annum. About 1 milliSievert of that is external radiation from X-rays and gamma rays. At 1 milliSievert of whole-body exposure, every cell nucleus in the human body is crossed by, on average, one X-ray/gamma-ray per year. This will cause, on average, 4 double-strand breaks per hundred cells, 15 DNA crosslink breaks per hundred cells, 100 single-strand breaks per hundred cells, and 250 damaged DNA base-molecules per hundred cells.

The most damaging type of radiation to biological material is ionising radiation. This is radiation which possesses sufficient energy to liberate the electrons from the host atoms or molecules in biological tissue. X-rays and gamma rays are ionising radiation, which deposit their energy indirectly in biological material. That is, they create secondary charged particles, typically electrons, which deposit their energy by means of the direct ionisation and excitation of the atoms and molecules in the biological medium.

An X-ray or gamma ray photon can liberate an electron by means of either:

(i) the photoelectric effect, in which a tightly bound inner electron is freed from its atom, and the photon is absorbed;

(ii) Compton scattering, in which the photon transfers some of its energy to free a loosely-held outer electron;

(iii) pair production, in which the photon interacts with the electrostatic field of an atomic nucleus, and is converted into an electron and a positron.

Once a secondary particle is created by this means, it can typically undergo millions of Coulomb force interactions with other atoms and molecules before it loses all its kinetic energy, exciting and ionising those atoms and molecules en route. A high-energy electron can sometimes also lose energy by bremsstrahlung X-ray production, if accelerated by a nearby atomic nucleus. This X-ray may, in turn, ionise other atoms, or may simply exit the biological medium. Within the trail of ionised atoms created by an electron, those atoms which have lost an electron from an inner shell may themselves emit fluorescent radiation, or may emit a cascade of low-energy Auger electrons.

There's a lot going on, then.

In addition to the complexity of the particle interactions, it is necessary to consider the complex levels of DNA structure within a cell nucleus. The DNA double helix is wound around spools of protein called histones. The spools are themselves linked together, and the DNA winds one and a half-times around each histone to form what's called a nucleosome. The nucleosomes are then wound into a spiral structure themselves, and this spiral forms loops attached to so-called protein scaffolding.

Whilst there is obviously an enormous amount of complexity here, I don't see much evidence of ambitious theoretical and mathematical programmes within the field of oncology. Too much research time and money is expended on trial-and-error experimentation. What we need is a decent theoretical model of all the structures and processes involved in the formation of cancer, and then we need a supercomputer simulation, or distributed computing simulation of these structures and processes. Without wishing to trivialise the difficulty involved, the field of oncology needs something comparable to the Millennium simulation in cosmology.


Clare Dudman said...

Fascinating. I've always thought that the in-between structures (between DNA and chromosomes) are too much ignored.

Gordon McCabe said...

Indeed, chromatin fibre, as I neglected to mention it's called.