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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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« Aneuploidy, or What're A Few Chromosomes, More or Less? | Main | How Not to Do It: Solvent Stills »

August 28, 2002

Consequences of Aneuploidy

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Posted by Derek

Man, with headlines like that, I can't think of why I'm not pulling in thousands of hits a day. Anyway, I wanted to follow up on yesterday's posting by emphasizing that aneuploidy hasn't been ignored for all these years. It's just that the chicken-and-egg question about its role in cancer is heating up.

For example, the "micronucleus test" is often done alongside the Ames test. It's a direct measurement for this sort of chromosome breakage and malformation. The "micronucleus test" can be done with various cell lines, but one popular method is to administer the compounds to rodents and check their red blood cells (erythrocytes.) This looks at the effects on the precursor bone marrow stem cells, and depends on the odd fact that erythrocytes have their nucleus removed while they're developing.

If severe genomic damage occurs, odds and ends of chromosomes often end up lumped together in a separate "micronucleus" floating around detached from the main one. The micronucleus doesn't get pushed out of the erythrocyte, though, and it ends up standing out dramatically in a finished red blood cell. You can do such tests on other cells in culture as well, but those variations haven't been as well validated as the in vivo one.

If there are human cells with a tendency towards induced aneuploidy (as Duesberg and others claim) then there are some new possibilities for a useful screening test. One hitch might be that cultured cell lines often forget their origins after a while and act differently - not being exposed to all the various extracellular signals they're used to probably explains a lot of this. It's worth a look, though, particularly if aneuploidy does turn out to be an early event in carcinogenesis.

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