From: matus (matus@matus1976.com)
Date: Sat Sep 13 2003 - 09:18:56 MDT
>-----Original Message-----
>From: Robert J. Bradbury
>
>> It takes *at least* five mutations for a cell to become
>cancerous, 50%
>> of cancerous cells have a mutation in the p53 gene, if one of your
>> parents gamete cells has that mutation, you are far more
>likely to get
>> cancer throughout your lifetime then people without that mutation.
>
>Actually Michael, this may not be strictly true -- yes the p53
>gene and retinoblastoma (RB gene) mutations do certainly bias
>cells towards cancer. The standard "5 mutations" model is
>used mainly with colon cancer I believe. But there are other
>types of cancer, esp. leukemia where the primary culprit is
>chromosome rearrangements (do a google on "Philadelphia
>Chromosome").
Robert, thanks for the excellent info. I find this topic very
interesting and will certainly do the research you suggest. I did not
think the 'five mutation' model was completely accurate in all cases,
but from the rest of your descriptions, it seems it, or something very
similar, is the case in most forms of cancer with the exception being
luekemia. I will definitely read up on the biological processes
responsible for leukemia.
>
>I think the counts at this point are something like 15-20
>tumor suppressor genes (like p53 and RB) and perhaps 50-100
>tumor promoter genes. One generally has to get mutations in
>several of the tumor promoter genes and 1 or more of the tumor
>supressor genes before the cell becomes cancerous.
So the five mutation model may not describe every form of cellular
cancer, there are probably four mutation or eight mutation variants?
The number of mutations may differ, but is seems safe to say the
principle and the requirement for certain number of certain mutations to
take place is still valid.
The p53
>gene is a particular weak point because it seems it plays a
>critical part of deciding whether the cell should commit apoptosis
>(suicide) if things get too messed up.
>
>> Its not just any five mutations, but a whole score of mutations can
>> occur in different places in the genome.
>
>Yes, but I would probably say that each specific type of
>cancer results from an accumulation of a specific set of
>mutations (or genomic changes) that cause the normal cellular
>control processes to become defective. That is why you can
>view aging in part of the flip side of the coin from cancer.
>We *know* from cancer research that mutations and chromosomal
>rearrangements are taking place. One has to ask what kind of
>damage results from the same types of mutations and
>rearrangements taking place in those genes that are not
>involved in tumor suppression or tumor promotion? If one has
>a few hundred genes involved in regulating cell division then
>one has 30,000+ genes involved in dealing with other stuff.
>What happens as they gradually go bad?
>
>
>> At least five of the target areas have to be mutation.
>
>Not strictly true as pointed out above.
>
>> Eventually, all cells in
>> your body (with the exception of nuerons) are child cells of parents,
>
>Not quite accurate. Obviously all the cells in your body are
>the child cells of parent cells. Different cells in your body
>have different regenerative schedules.
My main point was that once a cell gets a mutation, all of its offspring
have that same mutation (unless some are lucky enough to have that
mutation reversed accidently) Thus the older you get, the more likely
you are to have more of your cells have more and more mutations, even in
the absence of pollution or radiation.
>
>So one can view tissues that are biased towards cellular
>division as already having a genetic program with a few
>"mutations" that can lead down the path to cancer. (When was
>the last time you heard of someone getting "heart cancer"?)
Never have, actually. Interesting stuff.
>
>Now, dealing with Robbie's claims -- I would suggest that you
>go do a google on "aflatoxin grain cancer". Aflatoxin is a
>toxin produced by a natural fungus that is known to cause a specific
>mutation(s) in the p53 gene. It is a primary source of liver
>cancer in China which has few or no constraints on the levels
>of aflatoxin that may be present in grains or peanuts (which
>are particularly susceptible to the fungus). Now could you
>please explain how a toxin produced by a natural fungus can be
>considered a "pollutant"?
I think this question was rhetorical, I have been saying all along that
natural sources contribute to far more cases of cancers than man made
pollutants or radiation. Since virtually all plants we eat are pumped
full of natural pesticides. Whether or not natural pesticides or toxins
should be called 'pollutants' seems more of a semantic issue, though I
would answer no to that.
Robbie, is a natural toxin a 'pollutant'?
>The rise in exposure to aflatoxin is
>a consequence of the fact that over the last several thousand
>years humans learned to store food sources to allow them to
>survive years when crop harvests are poor. So you can die from
>starvation or you may eventually die from cancer due to long
>term aflatoxin exposure. Take your pick.
I am sure there are many more examples like the one you cite, and
probably many that have nothing to do with human behavior. It has been
only very recently that the EPA has payed *any* attention at all to
natural carcinogens. Too busy obsessed with placing all the blame on
'evil corporations' as Robbie seems to be, instead of actually trying to
get an accurate description of reality.
>
>I am not saying that there is not any evidence that pollutants
>do not contribute to cancer. For example, there is
>overwhelming evidence that some of the substances in tobacco
>smoke -- which one can probably consider to be a pollutant --
>do contribute to mutations and cancer in a significant subset
>of the human population (in large part due to their genetic
>makeup most probably). However other pollutants, such as
>lead, may have little relation to cancer but may instead
>impact other functions such a neuronal development or activity.
>
I am sure there are many made made pollutants which are specifically
carcinogenic, but I don't think I would consider smoking in that
category, since it is generally a chosen behavior (pollutant as in
something people get subjected to against their preferences) But again,
I will continue to argue unless presented with evidence suggesting
otherwise that the vast majority of cancers come from diet, both what we
eat and how much of it, and for how long we have been eating it.
All this talk of Diet and cancer makes me want to stop procrastinating
and do a CR diet.
Michael Dickey
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