Cancer and gene mutation: A real or fictious relationship?

Discussion in 'Health and medical' started by Cncabej, Mar 13, 2004.

  1. Cncabej

    Cncabej Guest

    Cancer is generally considered to be an abnormal growth of
    cells caused by mutations in DNA induced by carcinogenic
    substances, viral oncogenes, ionizing radiations etc.
    Although evidence has been insufficient, and it has also
    been argued that often this relationship was not seen, the
    mutational theory of cancer is the explanation we find in
    every textbook. A recent experiment raises doubts about the
    validity of the dogma. Investigators show that mutation in
    the Ha-ras-1 gene is sometime found in normal mammary gland
    and is absent in cancerous cells. Here is the abstract
    published in the Journal of Cell Science on March , 2 2004.

    THE STROMA AS A CRUCIAL TARGET IN RAT MAMMARY GLAND
    CARCINOGENESIS

    Maricel V. Maffini1, Ana M. Soto1,*, Janine M. Calabro1,
    Angelo A. Ucci2 and Carlos Sonnenschein1

    A complex network of interactions between the stroma, the
    extracellular matrix and the epithelium drives mammary gland
    development and function. Two main assumptions in chemical
    carcinogenesis of the mammary gland have been that
    carcinogens induce neoplasia by causing mutations in the DNA
    of the epithelial cells and that the alterations of tissue
    architecture observed in neoplasms are a consequence of this
    primary mutational event. Here, we use a rat mammary tissue
    recombination model and the chemical carcinogen N-
    nitrosomethylurea (NMU) to determine whether the primary
    target of the carcinogen is the epithelium, the stroma or
    both tissue compartments. Mammary epithelial cells were
    exposed in vitro either to the carcinogen or vehicle before
    being transplanted into the cleared fat pads of rats exposed
    to carcinogen or vehicle. We observed that neoplastic
    transformation of these mammary epithelial cells occurred
    only when the stroma was exposed in vivo to NMU, regardless
    of whether or not the epithelial cells were exposed to the
    carcinogen. Mammary epithelial cells exposed in vitro to the
    carcinogen formed phenotypically normal ducts when injected
    into a non-treated stroma. Mutation in the Ha-ras-1 gene did
    not correlate with initiation of neoplasia. Not only was it
    often found in both cleared mammary fat pads of vehicle-
    treated animals and intact mammary glands of untreated
    animals, but it was also absent in some tumors. Our results
    suggest that the stroma is a crucial target of the
    carcinogen and that mutation in the Ha-ras-1 gene is neither
    necessary nor sufficient for tumor initiation.

    I am not predicting (although I am not excluding) that this
    will start a chain reaction of experiments designed to prove
    the EPIGENETIC origin of cancer, but it should make us
    rethink what is real (production of proteins) and what is
    fictious (determination of morphology, etiology of diseases,
    etc.) on the role of genes in biology.
     
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  2. << Cancer is generally considered to be an abnormal growth
    of cells caused by mutations in DNA induced by carcinogenic
    substances, viral oncogenes, ionizing radiations etc. >>

    Let me say this cautiously.

    Yet it has also been found that many cancer patients share
    some basic psychological behaviors. Why would that be if
    those psychological behaviors didn't in some way connect
    with the disease?

    Anyone studying a chronic disease that develops over long
    periods of time, and that seems to have a strong
    psychological aspect accompanying it ; should take that into
    account when attacking the disease - everything should be on
    the table in attacking cancer IMO.

    In the case of some cancer (those not proven to be caused by
    carcinogens) there seems to often be a stoic behavior in the
    patient, an anger at self, a strong guilt, repressed fears
    in some cases, etc. Is that a reflection of the body's
    response to the disease, or a cause that is partially
    responsible.

    We know of cases of diseases in which the self not only
    attacks the non-self within the body, but it wrongly attacks
    the self within the body too as sort of an over protection
    that has gone amok. Where does cancer fit in here?
     
  3. Tim Tyler

    Tim Tyler Guest

    CNCabej <[email protected]> wrote or quoted:

    > Cancer is generally considered to be an abnormal growth of
    > cells caused by mutations in DNA induced by carcinogenic
    > substances, viral oncogenes, ionizing radiations etc.
    > Although evidence has been insufficient, and it has also
    > been argued that often this relationship was not seen, the
    > mutational theory of cancer is the explanation we find in
    > every textbook. A recent experiment raises doubts about
    > the validity of the dogma. Investigators show that
    > mutation in the Ha-ras-1 gene is sometime found in normal
    > mammary gland and is absent in cancerous cells.

    "[...] it was also absent in *some* tumors" is what
    they wrote.

    I.e. this particular mutation was probably not the sole
    causal factor.

    > Here is the abstract published in the Journal of Cell
    > Science on March , 2 2004.
    >
    > THE STROMA AS A CRUCIAL TARGET IN RAT MAMMARY GLAND
    > CARCINOGENESIS
    >
    > Maricel V. Maffini1, Ana M. Soto1,*, Janine M. Calabro1,
    > Angelo A. Ucci2 and Carlos Sonnenschein1
    >
    > A complex network of interactions between the stroma, the
    > extracellular matrix and the epithelium drives mammary
    > gland development and function. Two main assumptions in
    > chemical carcinogenesis of the mammary gland have been
    > that carcinogens induce neoplasia by causing mutations in
    > the DNA of the epithelial cells and that the alterations
    > of tissue architecture observed in neoplasms are a
    > consequence of this primary mutational event. Here, we use
    > a rat mammary tissue recombination model and the chemical
    > carcinogen N-nitrosomethylurea (NMU) to determine whether
    > the primary target of the carcinogen is the epithelium,
    > the stroma or both tissue compartments. Mammary epithelial
    > cells were exposed in vitro either to the carcinogen or
    > vehicle before being transplanted into the cleared fat
    > pads of rats exposed to carcinogen or vehicle. We observed
    > that neoplastic transformation of these mammary epithelial
    > cells occurred only when the stroma was exposed in vivo to
    > NMU, regardless of whether or not the epithelial cells
    > were exposed to the carcinogen. Mammary epithelial cells
    > exposed in vitro to the carcinogen formed phenotypically
    > normal ducts when injected into a non-treated stroma.
    > Mutation in the Ha-ras-1 gene did not correlate with
    > initiation of neoplasia. Not only was it often found in
    > both cleared mammary fat pads of vehicle-treated animals
    > and intact mammary glands of untreated animals, but it was
    > also absent in some tumors. Our results suggest that the
    > stroma is a crucial target of the carcinogen and that
    > mutation in the Ha-ras-1 gene is neither necessary nor
    > sufficient for tumor initiation.
    >
    >
    > I am not predicting (although I am not excluding) that
    > this will start a chain reaction of experiments designed
    > to prove the EPIGENETIC origin of cancer, but it should
    > make us rethink what is real (production of proteins) and
    > what is fictious (determination of morphology, etiology of
    > diseases, etc.) on the role of genes in biology.

    I'm not sure I understand.

    Isn't cancer thought to be caused by (among other things)
    radiation.

    It seems to me that radiation qualifies as "EPIGENETIC"
    in origin.

    I certainly can't see anything very revolutionary in the
    study you cite.

    I don't see how it raises any doubts at all about the
    validity of the conventional explanations for cancer.
    --
    __________
    |im |yler http://timtyler.org/ [email protected] Remove
    lock to reply.
     
  4. [email protected] (CNCabej) wrote in
    news:[email protected]:

    > Cancer is generally considered to be an abnormal growth of
    > cells caused by mutations in DNA induced by carcinogenic
    > substances, viral oncogenes, ionizing radiations etc.
    > Although evidence has been insufficient, and it has also
    > been argued that often this relationship was not seen, the
    > mutational theory of cancer is the explanation we find in
    > every textbook. A recent experiment raises doubts about
    > the validity of the dogma. Investigators show that
    > mutation in the Ha-ras-1 gene is sometime found in normal
    > mammary gland and is absent in cancerous cells. Here is
    > the abstract published in the Journal of Cell Science on
    > March , 2 2004.

    (snip)

    > Our results suggest that the stroma is a crucial target of
    > the carcinogen and that mutation in the Ha-ras-1 gene is
    > neither necessary nor sufficient for tumor initiation.

    > I am not predicting (although I am not excluding) that
    > this will start a chain reaction of experiments designed
    > to prove the EPIGENETIC origin of cancer, but it should
    > make us rethink what is real (production of proteins) and
    > what is fictious (determination of morphology, etiology of
    > diseases, etc.) on the role of genes in biology.

    The article, as I read it, has nothing to do with
    epigenetic origins of cancer.It simply says that the
    changes leading to the cancer occur in stromal cells rather
    than epithelial cells.

    Yours,

    Bill Morse
     
  5. Peter F.

    Peter F. Guest

    "CNCabej" <[email protected]> wrote in message
    news:[email protected]...
    > Cancer is generally considered to be an abnormal growth of
    > cells caused by mutations in DNA induced by carcinogenic
    > substances, viral oncogenes,
    ionizing
    > radiations etc. Although evidence has been insufficient,
    > and it has also
    been
    > argued that often this relationship was not seen, the
    > mutational theory of cancer is the explanation we find in
    > every textbook. A recent experiment
    raises
    > doubts about the validity of the dogma. Investigators show
    > that mutation
    in the
    > Ha-ras-1 gene is sometime found in normal mammary gland
    > and is absent in cancerous cells. Here is the abstract
    > published in the Journal of Cell
    Science
    > on March , 2 2004.
    <snip>

    It might be helpful, to people trying to understand cancers
    at the level of DNA, to look at that cancers as a legacy of
    a specific adaptative behaviour arisen in to-us-animals-
    ancestral populations of (in total a trillion^2 or so?)
    amoebic (single-celled) individuals.

    The thence arisen (and of cancer "prototypal") adaptive
    behaviour (or response pattern) in question, can be
    described as:
    - A 'last ditch' gamble on reproducing an offspring (mutant
    clone) that is genetically altered to the effect that the
    impact of the frequently occurring "Inescapable
    'Irritating Cloud' Type Stressors/Situations", that
    trillions of amoebic individuals of ancestral population
    frequently got caught-up in, became neutral (not
    irritating), or even sometimes a source of nutrients, to
    the offspring's adaptively altered genophenotype.

    This 'inside-out' view of cancers came to me as a spin-off
    from when I tried to imagine a simplest possible case of
    being in a SHITS ["selective (as specific as synapse-
    situated) Hibernation" imploring type stressors/situations].

    There is of course to be an emphasis on the unifying meaning
    of the word "Irritating", and on the meaning of the "Cloud"
    as being vast and longterm enough to cause an amoebic
    creatures reflexive recoils form the Cloud's constituent
    irritants to soon become a decidedly mal-adaptive
    behavioural response (IOW the irritants would cause a futile
    expenditure of vital, potentially reproductive, energy).
    ----

    [Just for some SEPTIC humored and typically fuzzsilly
    logical EPT fun, try sounding the ICTS with a sloopy Cech
    pronounciation.%-].]
    ----

    P
     
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