The p53 tumor suppressor gene and guanine to thymine transversions, the plot thickens.

The main reason for this posting is so I do not lose the paper, “Analysis of radon associated squamous cell carcinomas of the lung for a p53 gene hotspot.”

The World Health Organization went out of its way to prove that active smoking caused lung cancer, (denied by tobacco companies) by inducing a genetic mutation of the p53 gene called a guanine to thymine (G to T)  transversion.  There are two base pairs that make up our DNA, adenine (A) which forms a base pair with thymine (T) and guanine (G) forms a base pair with cytosine (C).

What happens is that adenine  instead of pairing with thymine, it pairs with guanine, (please correct me if I am wrong.)  The purpose of the p53 gene is to detect and repair DNA damage and stop the multiplication of cancer cells.  Active smoking deactivates the p53 putting it simply. However the WHO also found that this happened “…rarely in lung cancers of non-smokers.”

However this new research I have uncovered suggests that the G to T transversion occurs in non smokers exposed to radon gas. In one Colorado mine  12 out of 41 cases were G to T transversions and  2 out of 38 in Saxony (Stollberg) Germany.

I have missed a portion out here but the anti smoking lobby maybe forced to admit that there has not been one death from lung cancer from passive smoking.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374385/pdf/82-6690995a.pdf

Advertisements
This entry was posted in Lung cancer, Smoking and tagged . Bookmark the permalink.

12 Responses to The p53 tumor suppressor gene and guanine to thymine transversions, the plot thickens.

  1. JJ says:

    Something that we have suspected all along Dave…however please keep us informed on this one. If cancer is caused by something that we breathe in, then people would be dying of lung cancer all the time. At some stage genetic mutation, (unconnected to smoking) will be understood to cause lung cancer.

    • Personally I think its a breakdown in the immune response as we age and in younger folks its probably the same thing that happens to the older folks!

      • Thats why its imperative to connect the dots from that first puff to cancer if thats the actual cause which I think it isnt. The only way to find cures is to understand what happens thru the whole process!

  2. Exactly and when they did this inducing a genetic mutation of the p53 gene called a guanine to thymine (G to T) transversion. What was the chemical used to make this mutation happen and at what dosage……whats the connection to tobacco?

    • daveatherton says:

      The chemical which causes the G to T transversion is benzo(a)pyrene a 5 ring benzene molecule.

      • Next question, What dosage level did they use to get it to happen compared to the listings of safe levels. This is important in constructing a model of cause, elapsed time of exposure,level of exposure etc……..What model did they use as in live tissue samples or what.

      • Another thing the assays that were tested were they all consistent or were only 20% positive etc!

  3. The former study where they had created a throat and induced smoke to it to proove smoking caused cancer was questioned on many levels. Mainly they did not state at what dose level the smoke was of what particular chemicals were in it during the study!

    The dose response is what may cause cancers from assumed carcinogens. This seems to always be left out and we can see why when only those 6-9% of life long smokers if ever get any cancers!

  4. Rose says:

    Dave

    In regards to the P53 gene I tried to give you this once before but you seemed annoyed, so if it’s really of no interest, please delete at will.

    Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis

    “Studies presented here show that cellular NAD, which we hypothesize to be the relevant biomarker of niacin status, is significantly lower in humans than in the commonly studied animal models of carcinogenesis”

    “We show that nicotinamide and the resulting cellular NAD concentration modulate expression of the tumor suppressor protein, p53, in human breast, skin, and lung cells.

    Studies to determine the optimal NAD concentrations for responding to DNA damage in breast epithelial cells reveal that DNA damage appears to stimulate NAD biosynthesis and that recovery from DNA damage occurs several hours earlier in the presence of higher NAD or in cells undergoing active NAD biosynthesis.

    Finally, analyses of normal human skin tissue from individuals diagnosed with actinic keratoses or squamous cell carcinomas show that NAD content of the skin is inversely correlated with the malignant phenotype.

    Since NAD is important in modulating ADP-ribose polymer metabolism, cyclic ADP-ribose synthesis, and stress response proteins, such as p53, following DNA damage, understanding how NAD metabolism is regulated in the human has important implications in developing both prevention and treatment strategies in carcinogenesis.”
    http://www.mentorwwllc.com/pdfs-global/nia/study/MappingroleofNADmetabolism.pdf

    Niacin deficiency and cancer in women
    “A new interest in the relationship between niacin and cancer has evolved from the discovery that the principal form of this vitamin, NAD, is consumed as a substrate in ADP-ribose transfer reactions. Poly(ADP-ribose) polymerase, an enzyme activated by DNA strand breaks, is the ADP-ribosyltransferase of greatest interest with regard to effects on the niacin status of cells since its Km for NAD is high, and its activity can deplete NAD. Studies of the consequences of DNA damage in cultured mouse and human cells as a function of niacin status have supported the hypothesis that niacin may be a protective factor that limits carcinogenic events”
    http://www.jacn.org/content/12/4/412.abstract

    Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide.
    “The current study was designed to determine whether topical nicotinamide, the active form of vitamin B-3, or niacin, prevents immunosuppression and skin cancer in UV-irradiated mice. In a passive transfer assay for immunosuppression, splenocytes from UV-irradiated mice enhanced the growth of antigenic tumor challenges in recipient mice. Treatment of the UV-irradiated mice with 40 mumol of nicotinamide twice weekly starting two weeks before UV irradiation and throughout the experiment prevented this immunosuppression.

    UVB irradiation consisted of five weekly 30-minute exposures to banks of six FS40 Westinghouse fluorescent sunlamps. Mice received approximately 6.2 x 10(5) J/m2 in the passive transfer assays and 1.09 x 10(6) J/m2 in the photocarcinogenesis studies. Application of nicotinamide to UV-irradiated mice reduced skin tumor incidence from 75% to 42.5% (p = 0.016, Cox proportional hazards analysis). Thus topical nicotinamide prevented the immunosuppression and skin tumor induction by UVB irradiation.
    http://www.medscape.com/medline/abstract/9427980

    NAD in skin: therapeutic approaches for niacin.

    “Furthermore, the identification of the nicotinic acid receptor in human skin keratinocytes provides a further link to niacin’s role as a potential skin cancer prevention agent and suggests the nicotinic acid receptor as a potential target for skin cancer prevention agents. The new roles for niacin as a modulator of differentiation and photo-immune suppression and niacin status as a critical resistance factor for UV damaged skin cells are reviewed here.”
    http://www.ncbi.nlm.nih.gov/pubmed/19149600

    Niacin and Niacinamide In Flue Cured Cigarette Smoke Condensate August 10 1960
    “The susceptibility of mice to lung adenomas, induced by urethran feeding, depends upon the dietary supply of niacin.
    Furthermore, Strain A mice, on a niacin deficient diet, showed a greatly increased incidence of spontaneous lung adenomas; whereas, a supplement of niacin seemed to be protective.”
    http://legacy.library.ucsf.edu/action/document/page?tid=pnx69d00&page=1

    Curious isn’t it?

    I kept on finding the same thing from different scientists under different circumstances as I investigated the plant.

    Trigonelline – coffee

    Anti-invasive activity of niacin and trigonelline against cancer cells.
    http://www.ncbi.nlm.nih.gov/pubmed/15785001

    Basic Chemical Reactions Occurring in the Roasting Process

    “The best cup characteristic are produced when the ratio of the degradation of trigonelline to the derivation of Nicotinic Acid remains linear.

    The control model of this reaction ratio is a time/temperature/energy relationship. The environment temperature (ET) establishes the pyrolysis region for the desired chemical reactions while the energy value (BTU) and system transfer efficiency (STE) determines the rate of reaction propagation and linearity of Nicotinic Acid derivation to degradation of trigonelline”
    http://www.sweetmarias.com/roast.carlstaub.html

    Coffee and cigarettes, who would have thought it? Beer too.

  5. Rose says:

    Trawling through this stuff for the last five years, I get the impression that the “principal” chemicals were really chosen by prohibitionists looking for the most horrible component in the things we enjoy just so they could complain about it and call people deviants.

    They were so horrified when nicotinic acid proved beneficial they changed the name.
    “Niacin was first discovered from the oxidation of nicotine to form nicotinic acid”.
    (By Huber in 1867)
    So the name was already fixed.

    “When the properties of nicotinic acid were discovered, it was thought prudent to choose a name to dissociate it from nicotine, in order to avoid the perception that vitamins or niacin-rich food contains nicotine. The resulting name ‘niacin’ was derived from nicotinic acid + vitamin.

    Niacin is also referred to as Vitamin B3 because it was the third of the B vitamins to be discovered. It has historically been referred to as “vitamin PP”, a name derived from the term “pellagra-preventing factor”.
    http://www.chemeurope.com/en/encyclopedia/Niacin.html

    By the AMA in 1942 apparently.
    Trouble is, not only have they confused the public, but it seems generations of scientists too.

    Parkinson’s protection without caffeine or nicotine

    “Decaf coffee and nicotine-free tobacco aren’t just for the health-conscious. Giving them to flies with a form of Parkinson’s disease has revealed that although coffee and cigarettes protect the brain, caffeine and nicotine aren’t responsible for the benefit.

    If the compounds that put up this brain defence can be identified, they may offer a preventive Parkinson’s treatment where none currently exists, says Leo Pallanck, a neuroscientist at the University of Washington in Seattle, whose team led the new study.

    “We think that there’s something else in coffee and tobacco that’s really important,” he says.”
    http://www.newscientist.com/article/dn18814-parkinsons-protection-without-caffeine-or-nicotine.html?DCMP=OTC-rss&nsref=online-news

    • Kathy says:

      enjoying tobacco does not make you get vitamin B3, vitamin B3 can be obtained by REACTING nicotine that is EXTRACTED from tobacco then PROCESSING it. You do not get niacin, vitamin B3 from smoking.

      Sorry, this isn’t a government cover up or whatever you think it is, smoking is still bad and you shouldn’t do it due to health reasons.

      However, tobacco is not a horrid plant, and it could be used for good things, but smoking it is a bad idea and bad for you.

  6. Rose says:

    Hi Dave,

    I just noticed something when I was going over some old notes.

    “However this new research I have uncovered suggests that the G to T transversion occurs in non smokers exposed to radon gas. In one Colorado mine 12 out of 41 cases were G to T transversions and 2 out of 38 in Saxony (Stollberg) Germany.

    I may have a match.

    “RESULTS: A relatively early age of lung cancer onset (ranging from 28 to 73 with a mean of 48) in mustard gas victims, particularly those in the non-smoking population (mean age of 40.7), may be an indication of a unique etiology for these cancers. Seven of the 20 patients developed lung cancer before the age of 40. Five of 16 cancers from which DNA sequence data was obtainable provided information on eight p53 mutations (within exons 5-8).

    These mutations were predominately G to A transitions; a mutation consistent with the DNA lesion caused by SM. Two of the lung cancers had multiple p53 point mutations, similar to results obtained from factory workers chronically exposed to mustard agent.”
    http://lib.bioinfo.pl/pmid:19559099

    My notes, if they are of any interest.
    http://tinyurl.com/3qy4au9

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s