Metastases and Carcinogens

"Welcome to hell, ladies. This is your first mission as a platoon commander. Don't screw it up. It's your job to manage the assault on the objective. All right devil dogs, saddle up and move out."
The sound of the colonel's voice blasting into my ears jarred me from my silent reverie. My first mission - this was it. The mission objectives were etched into my mind like a fossilised troglodyte. It had to be, because I'd just about memorised the entire mission briefing word for word. This was my first mission and it had to go perfectly, it just had to.
As my squad of assault vehicles trundled their way inexorably towards the designated waypoints, I ran the mission details through my mind once more - just to be sure.  Our objective was a malignant adenocarcinoma that had set itself up in the GIT. However, the intelligence reports coming in weren't good. There was evidence of metastases - a spread of a malignant tumour from its primary site, and they're as damned difficult to remove as two-day-old dog turd from combat boots.

Metastases can travel along 4 routes:
1.	Local invasion - this is direct growth into adjacent tissues and is the most common route of spread.
2.	Lymphatic spread - tumours can drain into lymph nodes, where they can start growing as secondary tumours. This is a common way for carcinomas to spread.
3.	Vascular spread - they can spread via the veins. GIT tumours often go to the liver through the portal vein. Tumours entering systemic veins can form metastases in the lung, bone marrow, brain and adrenal glands.
4.	Transcoelomic spread - Primary tumours in the abdominal cavity or thorax can spread via the coelomic spaces e.g. peritoneal or pleural cavities and migrate to the surface of other organs.

A priority signal from the scouts drove me rudely back to the present. "Report!" I barked into the radio as I tried as best as I could to appraise the situation. 
"We have encountered a cluster of metastatic cells, sir!" the voice on the radio came back. The tactical display in front of me lit up, indicating the size and position of the enemy forces.
"Shall we engage?" the radio crackled.
"Affirmative!" I bellowed. "You are free to engage the enemy. All right men, let's make the colonel proud."
Our vehicles moved into position and armed with our new guidance systems, we would have been fools to lose. It ended as quickly as it had started, and as predicted, the enemy was no match for us. Even so, adrenaline pumped through my body as I realised what had just happened. YES! This was it! My first victory! 

"Well done, Devil Dog. Proceed to your next encounter. Remember, you are a green amphibious monster. You are the finest killer on the battlefield. You eat barbed wire and you piss napalm."

My exultation was cut a little short. The colonel was right. We still had a job to do at the primary objective. Celebrations can come later. As our vehicles turned towards our next waypoint, though, I was still in high spirits. The tumour was as good as destroyed. 
Time spent in reconnaissance is seldom wasted, and that was certainly the case in this mission. "All right, listen up." It was the colonel. "The intelligence boys analysing the metastases turned up something interesting. Info's coming through on your display. Stand by."
It didn't take long for the words to appear on the screen: 
You may have heard that tumours metastasise in response to a specific selection pressure for them to do so. The result would be cells best equipped to invade and colonise other sites. They would have special mutations to produce more proteases to digest basement membranes, and motility factors to move faster and also to alter or lose cell adhesion molecules so they stick less well to certain tissues and better to target tissues. Well folks, I can tell you that we have seen NO hard evidence to support this view. The mutations found in metastatic malignant tumours are not much different to those found in the pre-malignant stage.
We believe that the enemy may be much less directed. With an accumulation of enough growth-control mutations of the same type found in non-invasive tumours, a cell may find itself able to grow in an inappropriate environment. A normal cell would kill itself if it entered an alien environment. This is due to cell-cell signalling and adhesion mechanisms that normally control tissue architecture. If a cell with these mechanisms disabled ended up in surrounding connective tissue or a blood vessel through trauma or tissue damage, it would simply keep growing.
Metastasis is very inefficient - most cells released from a tumour into a vessel die. Cells from metastases are not in general more metastatic, when reinjected in experimental animals, than cells from the primary tumour. This suggests that once a primary tumour invades locally, it is capable of metastasis, but the actual formation of metastases is a very inefficient one.
 
	I scarcely had time to digest this information when my tactical display lit up again. "Sir, upcoming threats on the scanner. Shall we engage, sir?"
"Negative. Don't waste your ammo on those dead men." I said as I studied the screen. "Hang back - I'll call for an arty strike." I radioed my priority request for the artillery strike on the enemy position and waited. The enemy was too well dug in for a simple assault, and I reckoned they needed a bit of softening up. 
The ground was ripped asunder as it rained hot artillery fire. As soon as the thunder from the explosions subsided, we rolled in like armoured behemoths from hell. They didn't know what hit them and it was all over before I could even feel sorry for them.
"The enemy units are no longer a threat, sir," the scouts reported even before the dust started to settle. Well, this was becoming a little too easy.
"Let's move on to our next objective. I wanna get back in time for lunch." I said.

"You are hard. You are fair. You only kill those who deserve to be killed. Remember - blood makes the grass grow."

	The colonel's words echoed in my head for a bit, settled down and took up residence in that place where those annoying bits of music go to repeat themselves over and over again. If you listen to the man for too long, you'll actually start believing that crap he's spouting. To take my mind off the propaganda and to ease my nerves somewhat, I punched in a request for the causes of cancer. I didn't have to wait long for the data to appear:

Agents that directly damage DNA	Radiation
UV light
Mutagenic chemicals	
Agents that don't directly damage DNA	Non-mutagenic chemicals or 'promoters'	
Tumour viruses		
Other causes	Chronic irritation, damage to tissue or abnormally high cell turnover
Abberrations of DNA replication and cell division.	

It also told me that agents that damaged the DNA, the 'initiators', need 'promoters' at above a certain dose for the tumour to develop. Following through on this, I called up a list of naturally occurring and dietary carcinogens. I wasn't disappointed.

Substrate	Source	
Mould carcinogen (aflatoxin, sterigmatocystin)	Mouldy grain, stored food, fruit and fruit juices	
Pyrolysis products (heterocyclic amines, polycyclic aromatic hydrocarbons)	Baked, grilled or charred food	
N-Nitrosoamino products	Cured meat, beer	
Spice flavours (saffrole, estragole)	Many edible plants, spices	
Hydrazines	Mushrooms, Cycad Nuts	
Furocoumarins	Celery, parsnip, figs	
Flavonoids
Quercitin
Theobromine	
Fruit and vegetables
Cocoa	

	It was with this on my mind when we finally approached the enemy field base. "All right men," I barked into the radio, "Hang back while I call in some close air support. The air support will recon the target area and suppress the enemy. This will allow us to roll right through the opposition."
	After what seemed like an eternity and a half, the sky suddenly filled with raining death as the air support wreaked havoc on the malignant cells. "OK men, let's move in and finish what we came here to do. I hope air support left something for us. Stick to the game plan and don't take undue risks. Get ready, we're going in."
	This was it. The final assault. With all the new weapons and the superiority there was always that doubt niggling away at the back of my mind that something might go wrong. The cells might have developed some sort of resistance, or they might have metastasised so much that would be too many of them to fight. I caught myself just in time. It's thoughts like these that would lead to failure. With such doubt, the battle would have been half lost already. In this game you have to be positive, you have to know that you will succeed - no matter what. Even if we don't get what we want in the end, we know we gave it our best shot.
	We charged straight in, guns blazing. I don't know how long it took. The weaponry did its worst on the cancerous cells. Many were destroyed, annihilated, obliterated - whatever word you like to use - but we couldn't stop. To be sure of victory, we couldn't afford to let even one get through. Even when the firing did stop, the explosions still rang in my ears. Sweat poured down my brow, and it was only after the last one was destroyed did I heave one massive sigh of relief and allow myself to relax. It was done. It was over! Success! Victory was ours!

	The loudspeaker crackled once more as the colonel spoke his piece:
"Congratulations, parade, you have successfully completed your mission. I will see you back at base. All right Devil Dog, you made it. Time to go, find some targets and destroy. You are a killer, you are an administrator of death. You will find the enemy - you will destroy it. I have given you the tools that you need to decimate the enemy. You will make me proud. Do you understand?"
"If it ain't broke, break it!"
-	When you break up an old system, it will likely come back together in a superior form. Your brain works on this principle of  'creative destruction' and it increases in elegance in proportion to the amount of disorder it's called upon to resolve.