One of my best friends is very, very smart. But also very very opinionated.😀 I was trying to describe a complex biological process and he says “I don’t care” and walks away. Now he’s very very good at changing his opinion when he gets a new viewpoint. And that is why we are great friends. If he would make the effort to understand the process I was trying to describe I can guarantee that he would change his mind. But he can’t _yet_.😀
I would like to try to describe a biological system that some of you may be well aware of but others may be not. How do we identify carcinogens?
The newspapers tell you that science has decreed a certain chemical as “likely to be a carcinogen.” How does the news media’s version of “science” do that?🤔
It’s called the Ames test. And what Bruce Ames wanted to do was find a way to detect mutations. He took a strain of bacteria that could grow fine with basically sugar and nitrogen and some mineral nutrients. And then he damaged it’s ability to make an amino acid -histidine. Now this bacterial strain can only grow if you supply it with histidine.
Bacteria and our cells always have a background rate of mutation. If you take a drop of Ames’s creation (about 3X10^8 cells) 100 million! cells and spread it around on a petri plate with the basic nutrients and _no histidine_ the vast majority of the cells can’t grow however five or six cells will grow. These cells grow and grow, overnight all in one place, and become visible colonies. Five or six cells will form colonies in this case, because that is the normal rate at which mutations are occurring in 100 million cells.
You can count those colonies and count the mutation frequency. I’m trying to keep this simple and just give the idea behind it so don’t get too tangled up with numbers.
I googled and tried to find a “simple description of the Ames test” and unbelievably I couldn’t find one that I didn’t think was just way too complicated. But you can certainly Google it online. (Auxotrophs and heterotrophs geez what’s wrong with people 😀)
Now the DNA changes that make the bacterial strain unable to make histidine are _very specific_ and this is why Bruce Ames is given so much credit for developing it. There are a set of strains. Some strains have simple DNA changes and others more complex ones. But the general point is that if the cells are exposed to a mutagen and then (as above) 100 million cells are plated; 10, 100, even a thousand cells exposed to this mutagen will have been mutagenized and will form colonies just like above and can be counted.
At the lower end where it’s very close to normal background is where the fuzziness (maybe it is maybe it’s not) comes in. But if a thousand colonies pop up it’s definitely a mutagen. Most carcinogens turn out to be mutagens. if you get a thousand colonies the substance is designated a likely carcinogen.
There’s one additional trick. Our livers are trying to DEtoxify environmental chemicals. Unfortunately since they have not evolved with the latest greatest toxin they often metabolize today’s chemicals and drugs into problems. Mouse liver extracts metabolize chemicals as our livers would. And so to be sure that these liver breakdown products aren’t themselves carcinogens, liver extracts are required in the process. Turns out that there are a lot of cases where the original chemical was not a carcinogen but after being exposed to what our livers can do to it the chemical was turned into a carcinogen.😮
And here is my conspiracy theory 😀. 30 years ago my wife was in a plant research lab and started talking about some of her old research that was with plant extracts (like the liver extracts above) metabolizing common pesticides into carcinogens. I was interested and got reprints from her. Unfortunately I lost them when I lost my house. And, they are now gone from the internet. 😮 But the papers I read showed that plant extracts which had not been studied previously could metabolize common pesticides into carcinogens. I can’t find hide nor hair of the papers.🤔
Always the best to you all!
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