Monday, February 1, 2016

A Day or So in the Life of a Cell

Hormesis is not the action of radiation on a single isolated cell. But when a society of cells, such as an organ, is subjected to low-doses of radiation, protective action occurs.
Hormesis, as discussed in Chapter 4, is the stimulatory action of a low dose of an agent that would be poisonous in larger amounts. Two of the questions that come to mind in considering the radiation hormesis phenomenon are:

How does radiation affect the body?
What physiological processes could cause the hormetic effect?

Circle the Wagons

Many of us have heard that the problem with radiation stems from radioactive particles smashing into our cells, breaking up the genes, crushing chromosomes, and mutilating the DNA - thus causing a cell to grow wildly out of control, which we call a cancer. (If you didn't think that, there must be something wrong with you, because that's what most people think.") When visualizing such cellular violence, I suspect that most of us have some kind of model in mind. Mine was a golf ball-sized alpha particle crashing into a basketball-sized cell, trashing pencil-sized chromosomes - all relatively speaking, of course. In the worst case, there was the dreaded "double-strand break," whereby a golf ball would slice through both pencil-like DNA strands, leaving the cell with no template by which to repair the damage, as it normally would do. Call the oncologist.

When I learned a little more about what goes on in a cell during its workaday world - which we'll be getting to shortly - my model just wasn't making much sense. So I decided to look at the relative sizes of cells and their atomic enemies in hopes of being able to better imagine the processes that were going on during the collisions. It was surprising.

Let us consider an average animal cell, which is about 20 microns (millionths of a meter) in diameter, and hypothetically expand its cross-sectional area until it is the size of the field in Yankee stadium. And then let's take an alpha particle - the shot put or bowling ball of the radioactive world - and enlarge it in the same proportion. [The nuclei of all atoms are surprisingly close to the same size. Uranium, while more than 200 times heavier, is only about three times as large as a hydrogen atom. The nuclei of both are on the order of one barn in cross-section, with the bar being 10^-24 cm2. (The term was occasioned when an early researcher remarked that a particular element's cross section looked as "wide as a barn.")]

What would you think? The alpha particle would be the size of a dump truck? A Volkswagen? (Too big.) A volley-ball? A baseball? (Too big.) A pea? A B-B? (Too big.) The alpha particle, in relation to a Yankee-Stadium-sized-cell, would be about 0.0003 inches in diameter - nearly the same as a human hair.

So what about damage inflicted by beta particles and gamma rays?

Beta rays are just speedy electrons, with 1/1836 the mass of any one of the two protons and two neutrons making up an alpha particle. In terms of mass, the beta "particle" is a ping-pong ball compared with a 7.3-pound alpha-particle brick. When piercing our Yankee-Stadium-sized cell, the wound would be invisibly small, even with a magnifying glass. Say, maybe our cells aren't necessarily such wimpy victims after all.

Gamma rays and X-rays consist of photons, which, though devastating when loaded in Star Trek torpedoes, are "packets," or quanta, of energy that have essentially zero mass and therefore, zero size. [If you really want to be picky, the photon can be considered to have a mass because of the Einsteinian equivalency between mass and energy. But the photon exists in the form of energy and not mass as we know it.]

Neither of these forms of ionizing radiation would make anything like a visible hole in our Yankee-Stadium-sized cell, but would pass through the cell walls like light through a dirty window.

With respect to the cell as a whole, radiation seems like mosquitoes attacking a circus tent, but once inside, high-energy particles or rays can wreak havoc upon individual atoms and molecules that make up our cellular structure. Alpha particles, protons, and neutrons scatter whatever is in their path, using their mass energy to separate electrons from their parent nuclei. Beta rays whiz through a thin layer of cells, knocking other electrons out of their orbits until their rather limited energy is expended. Gamma and X-rays act similarly, but with a vengeance proportional to their energies and inversely proportional to their wavelengths. [Light, which is part of the same electromagnetic spectrum as both X-rays and gamma rays, behaves similarly. Long wavelength infrared light - otherwise known as radiant heat - has very little energy compared to short wavelength ultraviolet light... which can "ultraviolate" you on the beach if you don't use sunblock.]

Usually they still have plenty of spunk after zipping through our bodies, stripping some 10,000 electrons out of their formerly contented orbits in the process.

Whenever an electron and its former nucleus partner (the proton) are separated, the atom is ionized - with the electron being a negative ion and the electron-starved nucleus being a positive ion. While we've been taught that the dreaded "double-strand breaks" are the main problem, the cell has a way to take care of these, which we'll get to soon. The primary cause of cellular damage from ionizing radiation is, by gosh - ionization.

When an electron is stripped away from a water molecule - and these make up some 99% of a cell's cytoplasm (the stuff inside the cell's membrane but outside the nucleus) - the normally placid water molecule turns into the Mr. Hyde of the cellular world. Good old H2O is converted into strange entities like hydroxyl radicals (OH-), which will fight anybody or anything to hook up with another electron. These are the feared "free radicals," which are the targets of heroic "anti-oxidants" seen in all health food magazines.

Just as I was completely off base on my concept of relative sizes of atoms and cells, I also had misconceptions about cell activities. I assumed they lived a rather boring life interrupted occasionally by having to split into two cells. From time to time, however, a bullet of radiation might penetrate the cell, causing it to marshal its defenses - for a battle that would often be lost - and an almost inevitable cancer would result. It's not a totally irrational model if you've been led to believe that all radiation is hazardous. But it's not even close to being true.

Just in case your cellular biology is a bit rusty, let's look for a moment at a typical animal cell. It is surrounded by a membrane that somehow knows what substances to let into and out of the cell. Inside the cell - besides cytoplasm - is the nucleus, which contains the nucleoli and the chromosomes. (The nucleoli busy themselves making the RNA and protein.) Chromosomes are long, threadlike bodies consisting of a single DNA molecule coiled tightly inside. In humans, the molecule is thought to be around sixteen inches long, but so thin that it cannot be resolved with an electron microscope. [In the Yankee Stadium example, the DNA molecule would be about 4,000 miles long but possibly too thin to be seen with the naked eye.]

Only about 10% of the DNA is active in providing instructions for the cell's growth, functioning, and reproduction. The remainder (essentially archives of the cell's history) is sometimes referred to as "junk DNA."

As far as being a peaceful environment, the cell makes a beehive appear to be laid-back. There are roughly 200,000 DNA repairs every day in every cell with some 30,000 unrepaired breaks existing at any given time. About 2% of these are the dreaded-double-strand breaks.

So most of this is caused by radiation? Hardly.

Normal oxidative damage - arising from thermal instability, replication, and free-radicals spawned by normal cell activities - is the overwhelming cause of DNA alterations. For the average U.S. citizen receiving a background dose of 0.3 cSv (300 mrem), the radiation-produced DNA breaks number six per cell per year. Even a fatal dose of 1000 cGy (1,000,000 mrad) produces only 20,000 breaks per cell - a mere 0.03% of the normally occurring 70 million altercations per year.

It would appear from this that radiation should have little effect on us one way or the other. Insofar as directly causing cancer, that is indeed what the evidence in future chapters will show. As Theodore Rockwell puts it:

"It is the repair and removal process (or lack of it) that kills us. Like other toxins, high-level radiation degrades those processes, but low-level actually stimulates them." [Ted Rockwell, Sc.D. is the former technical director of U.S. Naval Reactors. The American Nuclear Society's Lifetime Contribution Award has been named the Rockwell Award in his honor.]

As anyone with the least familiarity with radiation knows, high levels of radiation are dangerous and can kill you (Table 8). The low-level effects may be new to you, but they are real and are arguably far more important for society than the almost infinitesimally rare occurrences of high-level exposures.

Table 8 – Acute Radiation Syndrome
Subclinical Range
0 – 100 rads
Therapeutic Range
100 – 500 rads
Lethal Range
500+ rads

100 – 200
200 – 300
300 – 500
500 – 2000
2000+
Appropriate Action
None
Clinical surveillance
Therapy effective
Therapy promising
Therapy palliative (comfort patient only)
Incidence of Vomiting
None
100 rads: 5%
200 rads: 50%
75%
75%
100%
100%
Delay Time
n/a
3 hours
2 hours
1 hour
3 min.
3 min.
Main Organs Affected
None
Blood Forming Tissue
Gastro-intestinal Tract
Central Nervous System
Characteristic Signs
None
White Blood Cell Decrease
Fatigue, infection, erythema, sterilization, loss of hair above 300 rads, hemorrhage
Diarrhea, fever, electrolyte imbalance, bleeding
Convulsion, coma, loss of muscle control, lethargy, tremors
Critical Period
n/a
n/a
4 – 6 weeks
5 – 14 days
1 – 48 hours
Post-exposure Therapy
Assure of Safety
Blood analysis; assure of safety
Blood transfusion; anti-biotics
Possible bone marrow transplant
Maintain electrolyte balance
Sedatives
Outlook
Excellent
Excellent
Good
Guarded
Hopeless
Hopeless
Convalescent Period
None
Several weeks
1 – 2 months
Long
n/a
n/a
Death Rate
None
None
0% - 40%
40% - 100%
90% - 100%
100%
Death Within
n/a
n/a
2 – 4 weeks
2 weeks
2 days
Cause of Death
n/a
n/a
Hemorrhage, infection
Dehydration
Respiratory failure; heart attack