#scitag

[mindshelter]

did you guys know there's a protein called sonic hedgehog. the researcher responsible thought it would be fun to use a character in the comic books his daughter owned. it's really important for healthy early development. and also a culprit for one subset of childhood brain cancer (among other malignancies), which is accordingly named sonic the hedgehog-driven medulloblastoma.

[mindshelter]

one thing that consistently happens when you sit in a room full of people who study disease is that one person will bring up an anecdote or fact out of a recent paper and another person will blurt out "that is so cool—no, not cool. it's not cool. it's ... interesting," when they realize their initial reaction makes them sound deranged

[mindshelter]

asked by @ghost-in-a-player-piano: Which body part is the biggest problem for using the badwrong instructions that can make cancer? Is it the liver? Since the liver can regrow itself as part of everyday normal business, I bet it's up there. extension of this thread.

oh! fantastic observation; with respect to liver cancers, this is a big area of discussion. you're right: tissue regeneration, by default, can predispose it to regenerating just a little too well. cancer emerging from hepatocytes (hepatocellular carcinoma), which make up most of the liver, is indeed one of the most common forms of adult cancer.

(note: it's up there, but not the furthest up! more on that later.)

i want to be a bit careful though: the liver's ability to regrow has the potential to influence cancer development, but that's one player among many.

we should consider what makes the liver a potential breeding ground for tumours beyond its powerful ability to regrow itself by asking why it's regrowing so much at all. existing liver tissue likely sustained some damage. this could be through a lot of means, such as excess alcohol consumption or hepatitis. damage means inflammation: tissue becomes swollen, and the affected tissue experiences something called oxidative stress.

you can think of oxidative stress as the production of very hostile molecules that carry oxygen atoms with the potential to mess up DNA. these reactive oxygen species are always present in the cells of the body, because oxygen is key to our ability to get the most energy possible out of sugar (glucose, specifically). they just exist at levels the body can handle. in cases like long-term inflammation, however, there's a fair chance they'll reach overwhelming levels.

the liver's efforts to regenerate are, ironically, an effort to resolve this inflammation—that's the organ trying to heal! however, when cells get ready to divide, they make copies of their DNA, and pass on new mistakes to their descendants. the source of the mistakes might come from the copying process itself, or it might come from our nasty reactive oxygen species hitting our DNA repeatedly until critical instructions get tampered with. following liver damage, both of these things are happening... so things might go awry.

so! chronic inflammation sounds like a big fucking deal, and it is. when it comes to body parts that are the "biggest problem for using the badwrong instructions," a noticeable pattern emerges: several are organs highly susceptible to inflammation. more common than liver cancer are lung cancer and colorectal cancer, to name two.

to showcase the phenomenon that is chronic inflammation in more concrete examples:

tobacco users are more susceptible to lung cancer; cigarette smoke irritates the lungs. that is, it induces inflammation.

asbestos is an extremely infamous cancer-causing substance. this is because asbestos, at the microscopic level, is made up of extremely small, sharp fibers. they quite literally can embed into lung cells and cause long-term inflammation. most often, it causes a form of cancer called malignant mesothelioma.

you'll never guess what inflammatory bowel disease can do. people affected tend to be prescribed anti-inflammatory medications, which both lowers the risk of colorectal cancer while reducing pain.

inflammation and growth capacity are, again, two among many things that can set a healthy cell down the path of evil, but they are extremely common culprits in the world of cancer.

thank you! i hope this was informative. hearts and love and all those nice things

[mindshelter]

questions by @stupidusernamepolicy! i'll answer these one by one.

Q: do carcinogens cause a specific mutation, or bring about random harm to the genome of a tissue that they're in close contact with?

A: a bit of both! in the context of the entire genome (def: all the DNA in a given cell), any part of it can sustain damage that produces errors. a carcinogen doesn't hone in on a specific gene and introduce mistakes, but it might only target specific nucleotides (def: DNA building blocks). UV radiation, for example, will hit the nucleotides thymine and cytosine, but not guanine and adenine.

another important thing to note is that while human DNA is linear, it's crumpled in this big harmonious mess in the cell nucleus so that everything can fit. i've noted elsewhere that a given cell has no need to access for all of its genes at a single moment. if we can think of our genome as a library, the books we are actively borrowing (loosely packed DNA that is being read) are at the biggest risk of being lost, damaged, etc. anything on the shelf (densely packed DNA) isn't impervious, but the likelihood that something will go wrong is somewhat lower.

therefore:

depending on the carcinogen, it is more likely to affect specific components of the genetic code.

however, it is not picky about where this component is. it is not trying to hit a specific gene.

that being said, DNA damage across the entire genome is not uniform. one reason among several is how densely a piece of DNA is packed in the cell.

Q: does that vary by carcinogen? like does asbestos just to whatever to DNA of lung tissue and fuck it up

A: yes, it varies! for this question, we should consider that there are two types of carcinogens from a biochemical perspective: direct and indirect. an example of a direct carcinogen is UV radiation—it hits the DNA itself. asbestos is indirect. it does not actually interact with DNA.

asbestos is, however, made out of long, microscopic fibres that can physically embed into the respiratory tract when inhaled. think millions of tiny needles. naturally, the lungs get irritated, and its tissue becomes inflamed. inflammation tends to produce reactive oxygen species (def: highly unstable oxygen-containing molecules) that then "attack" DNA.

Q: is a specific part of the genetic code more vulnerable to specific carcinogenic compounds in cigarette tar than others?

A: cigarette tar is a mixture of several carcinogens. some induce irritation (such as acrylonitrile), and therefore the formation of reactive oxygen species that can hit DNA. others are processed by the body into another, more dangerous form that can directly bind and damage DNA, like acrylamide.

like stated before, yup! some parts of the genetic code are more prone to sustaining damage than others, and this isn't a phenomenon restricted to a specific carcinogen. the actual distribution of how the genome gets hit is an active area of study. how the DNA is packed/where it is physically in the nucleus will influence how vulnerable it is, and this will vary by cell type.

the cell expects that its DNA will be damaged, and has cleanup teams that catch mistakes as they happen. these cleanup proteins are really, really good at their jobs! but when they're stretched thin with a lot of things to fix, they might prioritize things that are more important to cell function at a given moment. again, what's important will vary by cell type. (and i do wanna stress that this is still not entirely understood, so if this answer becomes contradictory to new evidence... well. that's science!)

[mindshelter]

@ghost-in-a-player-piano answering by reblog for readability! your understanding is correct, though not necessarily the full story: dysfunction that leads to excess cell division is what is required to make a tumour, but not all tumours are cancer. unintended growths happen, but they tend to be harmless. if they are removed, they never come back. where a tumour crosses a line to cancer is if the growth learns to spread, grow its own (usually shitty) blood vessels, damaging local tissue and, in many cases, starts invading other organs in a way that the body's natural defenses cannot adequately fight. removal isn't good enough because it's already sunken its claws into healthy tissue, and refuses to heed the body's orders to self-destruct.

which brings me to answering the questions asked. broadly, there's two ways cancer can get kickstarted: a gene important to cell growth and division becomes overactive, or a gene meant to stop growth/a suicide gene is turned off. in a given person, every cell they have now started from a single genetic blueprint. so, while this is an oversimplification, we would assume every healthy, noncancerous cell should have the same copies of the same versions of each gene.

and yes, that's part of why cancer can start pretty much anywhere. let's say a pancreas started off healthy (so yes, the person's genes did know how to make a normal organ), because it had the correct genetic instructions for most of the person's lifetime. somewhere down the line, a newer edition of the "How To Be A Good Pancreatic Cell" manual was put up, but it now had a critical mistake like "Grow Like Crazy Big," and maybe lost a page that said "If You Decide To Grow Like Crazy Big, Remember to Kill Yourself."

... or something of that nature. it's all downhill from there. this could have happened in the lungs, in the skin... you name it, but it happened in the pancreas instead, so it's pancreatic cancer.

there's a huge detail we can't neglect, however! if gene malfunction always produced the same problem everywhere... why are some forms of cancer more common than others? some considerations:

yes, every cell should have the same DNA, which encodes the same genes, which, when used, does something to the cell.

keyword: when used. some tissue types have no use for certain genes, while some require it for one reason or another. cells can also increase or decrease their use of a given gene as necessary.

keyword: does something to the cell. what that something is actually varies! genes always work in collaboration with other genes, and can be part of different cellular mechanisms.

this is precisely why we can start from a single cell, and then, over the course of gestation, grow a brain, lungs, a heart... and it's the same reason why some cancers are more common than others. the cancer-causing mutations (jargon: driver mutations/events) in one organ/tissue type are not necessarily what caused cancer in another location. hundreds of driver mutations have been documented; the "same" cancer in two different people might be fueled by different events—and they often are.

so, mutations do often boil down to happenstance. the likelihood that a given mutation becomes a problem, however, varies by tissue type.

i hope this was an adequate answer! as a final word, this is why cancer research is such a massive undertaking—and why it can be so mystifying of a concept to the layperson. if a "cure" for cancer is found, it's a relatively effective treatment for an iteration or two of the disease out of hundreds.

im so normal about genetics and the pathology of genetic diseases btw. like really normal <- about to combust and always happy to talk about it

[mindshelter]

a separate research group gave another protein—a cell growth regulator—the name POKEMON. it didn't stick because the company threatened to sue

did you guys know there's a protein called sonic hedgehog. the researcher responsible thought it would be fun to use a character in the comic books his daughter owned. it's really important for healthy early development. and also a culprit for one subset of childhood brain cancer (among other malignancies), which is accordingly named sonic the hedgehog-driven medulloblastoma.