OGG enzyme mediated genetic repair. A specific example of human variation to insult response.

That which is ascribed to probability or chance in studies of populations sometimes is actually a result of human variation due to both known and unknown mechanisms inherent within the individual, and the variations between individuals. For the most vulnerable, assurances of safety are particular lies. Here is one example. It is my view that polonium, present in cigarettes since the 1950s, is a major driver in tobacco related disease.


Partial quote.

Journal of the National Cancer Institute.
Oxford Journals
JNCI J Natl Cancer Inst
Volume 95, Issue 17
Pp. 1312-1319

DNA Repair Activity for Oxidative Damage and Risk of Lung Cancer

Tamar Paz-Elizur,
Meir Krupsky,
Sara Blumenstein,
Dalia Elinger,
Edna Schechtman and
Zvi Livneh

+ Author Affiliations

Affiliations of authors: T. Paz-Elizur, S. Blumenstein, D. Elinger, Z. Livneh, Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel; M. Krupsky, Pulmonary Institute, Sheba Medical Center, Tel Hashomer, Israel; E. Schechtman, Department of Industrial Engineering and Management, Ben Gurion University of the Negev, Beer Sheva, Israel.

Correspondence to: Zvi Livneh, PhD, Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel (e-mail: zvi.livneh@weizmann.ac.il).

Received July 30, 2002.
Revision received March 3, 2003.
Accepted June 25, 2003.


Background: Although smoking is a major cause of lung cancer, only a proportion of smokers develop lung cancer, suggesting a genetic predisposition in some individuals. Because tobacco smoking is associated with the increased formation of DNA lesions, including those induced from oxidative damage, we investigated whether the activity of the DNA repair enzyme 8-oxoguanine DNA N-glycosylase (OGG), which repairs the oxidative DNA lesion 8-oxoguanine, is associated with lung cancer. Methods: We conducted a molecular epidemiologic case–control study that included 68 case patients with non–small-cell lung cancer and 68 healthy control subjects, frequency matched for age and sex. Enzymatic OGG activity was determined in protein extracts prepared from peripheral blood mononuclear cells or lung tissue by assaying the cleavage product of a radiolabeled synthetic DNA oligonucleotide containing an 8-oxoguanine residue. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined by conditional logistic regression. All statistical tests were two-sided. Results: OGG activity was lower in peripheral blood mononuclear cells from case patients than in those from control subjects. After adjustment for age and smoking status, individuals in the lowest tertile of OGG activity had an increased risk of non–small-cell lung cancer compared with individuals in the highest tertile (OR = 4.8, 95% CI = 1.5 to 15.9). The adjusted OR associated with a unit decrease in OGG activity was statistically significantly increased (OR = 1.9, 95% CI = 1.3 to 2.8). There was no interaction between OGG activity and smoking status. The estimated relative risk of lung cancer for smokers with low OGG activity was 34- or 124-fold higher for smokers with a low OGG activity of 6.0 or 4.0 U/μg protein, respectively, than for nonsmokers with a normal OGG activity of 7.0 U/μg protein, illustrating the cumulative effect of low OGG activity and smoking. Conclusions: Low OGG activity is associated with an increased risk of lung cancer. Although prospective studies are needed to validate the results, they suggest that smoking cessation in individuals with reduced OGG activity might be an effective strategy in lung cancer prevention.

The high incidence and poor prognosis of lung cancer make it a major health problem worldwide (1–,3). A major cause of lung cancer is tobacco smoking, reflected by the fact that 80%–90% of lung cancer patients smoke (1). Although approximately 10% of heavy smokers (with more than 20 pack-years of smoking) develop lung cancer, the percentage of all smokers who develop lung cancer is substantially lower (4). This indicates that the carcinogenic effect of tobacco smoke affects only a fraction of those who smoke, most likely a result of differences in genetic predisposition to lung cancer (5–,7). The identification of genetic risk factors might be useful in lung cancer prevention.

Tobacco smoke contains multiple carcinogens that are known to chemically modify DNA (8) and lead to the formation of mutations (9). The accumulation of mutations in critical oncogenes and tumor suppressor genes promotes cancer (10). A critical cellular response that counteracts the carcinogenic effects of DNA damage is DNA repair (11). There are several known pathways of DNA repair, including base excision, nucleotide excision, and mismatch repair, all of which act to remove DNA lesions and prevent mutations, thereby restoring genetic integrity. The importance of DNA repair pathways is illustrated by a number of hereditary diseases, in which individuals with defects in DNA repair genes are highly susceptible to cancer. For example, defects in the nucleotide excision-repair pathway are associated with a high predisposition to skin cancer in patients with xeroderma pigmentosum (12), and defects in mismatch repair genes are associated with hereditary non-polyposis colorectal cancer (13).

Several studies have investigated whether reduced DNA repair is associated with lung cancer [reviewed in (14,,15)]. Reduced repair of benzo[a]pyrene DNA adducts, as measured by the host-cell reactivation assay, is associated with lung cancer (16). This method measures the expression of a reporter gene from a plasmid that has been treated with a DNA-damaging agent and introduced into cultured cells by transfection. The plasmids are repaired inside the cells, leading to increased gene expression. Because benzo[a]pyrene–DNA lesions are repaired via nucleotide excision repair, the degree of reporter gene expression is believed to reflect the activity of this repair pathway (17). In addition, reduced DNA repair of bleomycin-induced damage was found to be associated with lung cancer, using the comet assay (18). This method measures single-strand breaks in genomic DNA as a generalized measure of DNA repair activity, although it is difficult to relate that activity to specific DNA repair pathways. Nevertheless, these studies suggested that the reduced activity of various DNA repair mechanisms predisposes individuals to lung cancer and prompted us to search for defined DNA repair activities that may be risk factors for lung cancer. In particular, we sought to identify DNA repair mechanisms whose reduced activity predisposes smokers to lung cancer.

Because tobacco smoke induces the formation of oxidative DNA damage, we investigated whether reduced repair of oxidative DNA damage is associated with lung cancer. We focused on the repair of DNA containing 8-oxoguanine, a mutagenic lesion that is formed by oxidation (19), ionizing radiation (20), and tobacco smoke (21). 8-Oxoguanine is removed from DNA, primarily by base excision repair, in a process that is initiated by the enzyme 8-oxoguanine DNA N-glycosylase encoded by the OGG1 gene. This enzyme cleaves the bond linking the oxidized guanine to the deoxyribose and then breaks the DNA strand via its apurinic lyase activity [reviewed in (22)]. An additional DNA glycosylase with a similar activity is the recently discovered NEIL1; however, its activity is minor compared with that of the OGG1 gene product (23). In this study, we examined whether OGG activity is associated with non–small-cell lung cancer (NSCLC). …..

Low OGG activity is also associated with lung cancer in nonsmokers, although the estimated relative risk is much lower than in smokers. It seems possible that such individuals may reduce their risk of lung cancer by avoiding exposure to external sources of DNA damage, such as secondary smoke or ionizing radiation, and by modifying dietary habits to include known antioxidants that may reduce oxidative DNA damage. Although large population studies found that antioxidants did not reduce the risk of cancer (15,,33), whether these food additives might reduce the risk of cancer when used by individuals with low ability to repair oxidative DNA damage remains to be examined by future studies.


We thank Margaret Spitz (The University of Texas M. D. Anderson Cancer Center, Houston), Gad Rennert (Carmel Medical Center and the Technion Faculty of Medicine, Haifa, Israel) and Ofer Shpilberg (Ben Gurion University, Beer Sheva, Israel) for their help in epidemiologic issues, and Israel Parmet (Ben Gurion University) for his help with some of the calculations. ” end quote.

If you have low OGG activity, the crap broadcast by nuclear authorities in the wake of Fukushima and the creation, removal and contraction of evacuation zones in Japan are just more bullshit.

The human dose response to radiation exposure is individual, while nuclear authorities are only interested to the herd. If gunshot murders were investigated this way, no murder would be arrested.
It is still the case that most do not get shot. This does not in any way imply that guns are safe.

The uncontrolled release of nuclear industry’s “little bullets” (Pauling) also do not imply that nuclear industry is safe, the reverse is true. Any nuclear authority which cannot keep its sources sealed is demonstrably unsafe. None of them can.

The are probably many unknown variables in the human population. Individuals vary. The blanket proclamations of safety issued by nuclear authorities are crap. This individual variation has been known of for many decades.

Nuclear industry will defend itself against these facts by using concepts of eugenics. As they have in the past. Nuclear industry is anti- individual and anti democratic imo. For example, the Chair of the ICRP stated the following:

“Speaking at an atomic conference at Geneva, Sir Ernest Rock Carling, a Home Office pathologist, declared: “It is also to be hoped that, in a limited proportion of cases, these mutations (from nuclear radiation from atomic bomb test fallout) will have a favourable effect and produce a child of genius. At the risk of shocking this distinguished company, I affirm that the mutation that will give us an Aristotle, a Leonardo da Vinci, a Newton, a Pasteur, or an Einstein will largely compensate for the ninety nine others, which will have much less fortunate effects.” (cited by Pauwels and Bergier, 1960)

Confirmeation: Quote:
(UK) OHMS HANSARD 1803–2005 → 1950s → 1955 → November 1955 → 15 November 1955 → Commons Sitting → MINISTRY OF WORKS
Atoms for Peace Conference, Geneva
HC Deb 15 November 1955 vol 546 cc173-4 173
§ 10. Mr. Mason
asked the Minister of Works how many papers were presented at the Geneva Atoms for Peace Conference by British scientists and Government advisers; their titles; who presented them; and which were approved by Her Majesty’s Government.
§ Mr. Birch
The total number of British papers presented to the Conference was 99. I am placing in the Library a list of titles and authors of those papers which were read at the Conference. British scientists attended the Conference as individual experts, and they were not required to submit papers to Her Majesty’s Government for approval of the views expressed.
§ Mr. Mason
Could the Minister give an assurance that in the papers presented, particularly by people who have some responsibility to Her Majesty’s Government—for instance, Sir Ernest Rock Carling—no more theories are advanced as fantastically ridiculous as the one which he proposed?
§ Mr. Birch
Sir Ernest Rock Carling is not, of course, a member of a Government Department, and I have no need to answer for his views.
Back to Atomic Energy Authority (Uranium Supplies)

The Formation of the International Commission on Radiological Protection
1.4.2. Development into maturity
(10) Before the Second World War, the Committee (or Commission, as it was called from 1934) was not active between the ICRs, and met for just 1 day at the ICRs in Paris in 1931, Zu¨ rich in 1934, and Chicago in 1937.
(11) Lindell (1996a) noted that at the 1934 meeting in Zurich, the Commission was faced with undue pressures; the hosts insisted on four Swiss participants (out of a total of 11), and the German authorities replaced the Jewish German member with another person. In response to these pressures, the Commission decided on new rules in order to establish full control over its future membership.
(12) After the Second World War, the first post-war ICR convened in London in 1950. Just two of the members of IXRPC had survived the war, namely Lauriston Taylor and Rolf Sievert. Taylor was invited to revive and revise the Commission,
which was now given its present name: the International Commission on Radiological Protection (ICRP). Sievert remained an active member, Sir Ernest Rock Carling (UK) was appointed as Chairman, and Taylor was Acting Secretary; after the ICR, Walter Binks (UK) took over as Scientific Secretary because of Taylor’s concurrent
involvement with the sister organisation, ICRU.
(13) At the 1950 meeting, a new set of rules was drafted, quite similar to the present rules, for the work of ICRP and the selection of its members (ICRP, 1951), and six sub-committees were established on:
permissible dose for external radiation;
permissible dose for internal radiation;
protection against X rays generated at potentials up to 2 million volts;
protection against X rays above 2 million volts, and beta rays and gamma rays;
protection against heavy particles, including neutrons and protons; and
disposal of radioactive wastes and handling of radioisotopes.
Source: ICRP Publication 109, The History of ICRP and the Evolution of its Policies R.H. Clarke and J.Valentin
Invited by the Commission in October 2008
End quotes.

I am reminded that Baba et al and others found an increase in the rate of childhood cancer in Japan which commenced in the 1970s and did not stop increasing until after the 1980s. The state of the Japanese Cancer Registry, commenced only in 2006, and still for the most part non compulsory, is very poor compared to the USA and other modern nations. Nuclear industry commenced in Japan in the 1970s with a callous disregard for its emissions and the effects these may have upon the vulnerable. Cesium emissions from nuclear industry has been routinely measured in Japan for years.

When the time comes to compare the pre and post Fukushima nuclear disaster cancer statistics, as is normal (for instance there is no pre 1974 cancer registry data in Australia, so the actual effect of the bomb tests here is hidden from direct view) there will be a statistical deception of the same type used in the wake of other nuclear disaster. There will be a lowering of age of onset of disease among adults. In the case of Japan, where the ability to produce a decent statistical picture is limited apparently to Osaka only, there will be many opportunities for authorities to continue to mislead the public and for nuclear industry to deny responsibility. As that industry has done for many decades. It is time it stopped.

One Response to “OGG enzyme mediated genetic repair. A specific example of human variation to insult response.”

  1. CaptD Says:

    Hopefully modern technology will also help shine a light on Governmental “flim-flam” in the future!

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