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Metabolism Concentrated Hydrogen Isotope Chemi-Radiotherapy

The title needs work. I'll have words with the marketing department ASAP
  [vote for,

Cancer therapies attempt to kill or inhibit cancer cell growth. In general, the strategy has been to look at the features of cancer cells and try things that affect those more than the rest of the patient. This strategy works absolutely marvelously for antibiotics, because bacteria have many targets that do not exist in mammals, plants, mushrooms or even those dark patches in the least popular work bathroom.

Predictably, there is no universal difference between cancer cells and normal cells, hence no common target. Sure, they have mutated DNA, but so do most cells. Just bad luck on the regions. They like to grow, or at least that's a dangerous feature. But then so do the cells that are replacing skin. They run the full gamut of survival strategies available.

But, a sizable majority like to play silly buggers with metabolism. They're not interested in efficiency, and the tendency to politely kill themselves is a tendency that's weeded out by selection. For that reason, they distance themselves from their own mitochondria, reduce the total amount and involve them in as little as possible. This is because mitochondria are more than capable of killing the cell if they suspect any funny business. The cells still need them to make stuff, but they'd really rather they kept quiet and didn't interrupt the expansion plans up in management*.

Instead of an honest living, they prefer to gobble huge quantities of glucose, pyruvate and glutamine. Strategies to counter this are being tried, non-functional analogs of glucose and pyruvate exist and both work similarly. The greedy cells import them but they stop part way, yield no energy and then just, hang around. That's it. They specifically concentrate in the target, then not much else. A shocking waste of an opportunity.

Deuterium, hydrogen's chunky isotope brother, is more toxic to cancer cells than normal cells. That's because it disrupts the careful rearrangement of chromosomes during cell division... something cancer cells do more than most. Lots of drugs target cell division, but do not concentrate, or are actively excluded from cancer cells. So let's put a whole lot of deuterium onto our sneaky fake metabolite. I'm going with a deuterated version of 3- bromopyruvate**. But feel free to add deuterated 2-deoxyglucose and or glutamine. Now you are specifically targeting a cell division inhibitor to cells that are metabolically addicted to (one or more of) glucose, pyruvate and glutamine. The majority of cells will care not a jot.

For added value, go the whole hog*** and tritiate your metabolic analogs. Bioenergetic inhibition, cell division inhibition and local, concentrated radiotherapy.

*Feel free to substitute a superior mitochondrial metaphor, like I say, the marketing dept. has been under-performing.

**because it will preferentially hang around in the unusually alkaline cancer mitochondria.

***a tiny touch of 2,4,dnp and ketone supplementation should go further.

bs0u0155, Oct 26 2017

Tritium DNA damage http://www.tandfonl...0/09553007314550481
[bs0u0155, Oct 26 2017]


       Can Deuterium be selectively irradiated? as an added unchecked cell growth limiter.
wjt, Oct 26 2017

       I think the various conditions that can produce deuterium aren't really life-compatible.
bs0u0155, Oct 26 2017

       This seems like quite a good idea.   

       Out of interest, does deuterium interfere with DNA-related things, by modifying the hydrogen bonds between paired bases? Presumably any effect is small, but I wondered.
MaxwellBuchanan, Oct 26 2017

       Assuming there's a not-terribly complicated method of separating deuterium oxide from unoterium oxide, why not just drink the stuff ? and recycle. Some would be irretrievably lost to sweat, of course. [edit: 25%]
FlyingToaster, Oct 26 2017

       I think the point is to deuterate compounds that cancer cells are greedy for.   

       One other question, though - what's the rate of exchange of hydrogen (or deuterium) between things like glucose and things like water? Will your deuterium stay where it's meant to be? (I guess "yes" because tritium lebelling works.)
MaxwellBuchanan, Oct 26 2017

       // what's the rate of exchange of hydrogen (or deuterium) between things like glucose and things like water? //   

       Very low.   

       Sugars only weakly ionize in polar solvents, even though they're very soluble in water. As [bs] has pointed out, there's a plethora of explanations for the ionization of water, all of which account for the tendency of protons (or deuterons) to wander around without so much as a by-your-leave.   

       So in sugars, hydrogen atoms are quite firmly attached, hence the practicality of tritium labelling. But in water, the tritium nucleii can just bugger off any time they feel like it, which is a bit inconvenient.
8th of 7, Oct 26 2017

       //So in sugars, hydrogen atoms are quite firmly attached,//   

       ....and follow known paths through metabolism. It would be terrible if tritium were to concentrate within DNA. Tritium decay beta particles have a very short range in water, barely 1 cell diameter, so the global effects would likely be minimal. Sadly, for any unfortunate cells, those events could be quite catastrophic. <link>
bs0u0155, Oct 26 2017

       "it disrupts the careful rearrangement of chromosomes during cell division... something cancer cells do more than most"   

       But, if now normal cells, do sloppy re-arraignment only once, is that not still a problem?
mylodon, Oct 26 2017

       Nice, the knife edge between stopping cancers, and making new ones.   

       If a specific spectral pattern can be measured, can the reverse be done? , ping that specific pattern with a designed electromagnetic radiation.
wjt, Oct 26 2017

       //Nice, the knife edge between stopping cancers, and making new ones.//   

       The conventional therapies have very very significant problems with this already. It's rarely mentioned because it's assumed that the risk of dying of the cancer you have outweighs the risk of creating a new one and then dying of that. But consider that total body irradiation is still used, often combined with drugs that are used because they damage DNA. In a twisted way, that is an excellent recipe for cancer. The rationale is that rapidly proliferating cells, cancer/skin/blood cell precursors, are much more likely to be replicating their DNA, and are selectively vulnerable.   

       Targeting your anti-cancer system is a very attractive proposition, if you are sure where ALL of it is you can just chop it out/selectively irradiate it/inject it with something like alcohol which is an example of a chemical that's a brutal cell killer at 100% but just fine by the time it diffuses and dilutes out. You can't always find and kill all of it though.   

       So, it's much cleverer if you can somehow get the cancer to self target. An example of this is to be found in some thyroid cancers, the thyroid manufactures iodine-rich thyroxine and cancerous cells derived from the thyroid can be tricked with hormones into taking up all the iodine they can get. The trick is to sneakily replace the iodine with a radioactive substitute. The cancer (and remaining normal) thyroid cells dutifully concentrate the iodine within themselves, die and release the remaining radioactive iodine. This dilutes rapidly and is excreted so doesn't do too much damage, like mutating the DNA of a few hundred million cells.   

       //But, if now normal cells, do sloppy re-arraignment only once, is that not still a problem?//   

       There's a few features of long lived multicellular organisms that do an ALMOST perfect job of solving this problem. If DNA is damaged, it can be repaired good-as new. Problem solved. The repair can also be bodged, but the sloppy repair is in a section of DNA that doesn't matter to that cell. Or, the sloppy repair can be in a region that does matter to the cell, but the sloppy repair is good enough and nothing happens. Or, the sloppy repair happens in a critical part of DNA and now that bit doesn't work. Cell doesn't care, it has a back up chromosome. Now, if a lot of bad luck happens and some critical genes get turned off, and some damaged genes make stuck-in- the-on-position proteins there could be a problem. Fortunately, cells often spot this and politely retire or kill themselves. A replacement is usually arranged. If bad luck prevails, this is avoided, then the cell could have all the conditions to commence uncontrolled growth. Except that cell is so specialized it can't remember how do do that trick, such as the heart muscle cells or secretory cells of the pancreas. If it can remember and does start to divide, the immune system turns up and politely invites them to discontinue living.   

       There's a few additional checkpoints on top of those, like I say, the system is pretty thorough.
bs0u0155, Oct 27 2017

       //sloppy re-arraignment //   

       They need a better lawyer?
pertinax, Oct 30 2017


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