Protection of superoxide dismutase by caffeine in rat liver mitochondria against Ý-irradiation

Protection of superoxide dismutase by caffeine in rat liver mitochondria against Ý-irradiation
J. P. Kamat†, K. K. Boloor†,
T. P. A. Devasagayam† and P. C. Kesavan†,*,§

†Biosciences Group, Bhabha Atomic Research Centre, Trombay Mumbai 400 085, India

*M. S. Swaminathan Research Foundation, 3rd Cross Street,
Taramani Institutional Area, Chennai 600 113, India

Radiation is one of the physical agents that induce oxidative stress. Exposure of rat liver mitochondria to high doses of 60Co g -rays (45–600 Gy) results in the loss of activity of superoxide dismutase (SOD). Presence of caffeine, even in micromolar amounts, during exposure prevents loss of SOD activity. Caffeine, at a concentration of 1 mM also showed protection against radiation-induced inhibition of two other mitochondrial enzymes, namely succinate dehydrogenase and cytochrome c oxidase. The observed radioprotective ability of caffeine may be due to its ability to scavenge the reactive oxygen species generated by radiation and to inhibit radiation-induced membrane damage, as assessed by lipid peroxidation and protein oxidation.

OXIDATIVE stress that results from the increased generation of reactive oxygen species (ROS) has been implicated in major human ailments like cardiovascular disease, cancer and neural disorders and in the process of aging1,2. Ionizing radiation is a physical agent that induces oxidative stress by excess generation of ROS. With low Linear Energy Transfer (LET) radiation such as g -rays, most of the damage induced in biological systems is indirect and is mediated by ROS generated by the radiolytic products of water. These include hydroxyl radical (•OH), hydrogen atom (•H), hydrated electron (e_•aq), superoxide radicals (O2–•) and hydrogen peroxide (H2O2) (ref. 3). These reactive species are known to cause degradation of important macromolecules including DNA and membranes4,5. Among the sub-cellular organelles, mitochondria form some of the key components of cell killing induced by oxidative stress or radiation6,7. Though there are several antioxidant defences in the form of chemicals or enzymes, including those present in the mitochondria they are overwhelmed by high levels of pro-oxidants or radiation.

In the intracellular milieu, oxygen enhances radiation damage. The radiation-induced electrons react with oxygen to form superoxide anions (O2–•) (ref. 8) which have been implicated as important pathologic mediators

§For correspondence. (email: dae_hbc@mssrf.org)

in various disorders including cancer, inflammation or ischemia9. Superoxide dismutase (SOD) catalyses the dismutation of O2–• to H2O2 and O2, and thus it constitutes an early cellular defence against radiation and other forms of oxidative stress10,11. SOD has a high turnover and this provides a basis for maintain-ing the enzyme in active form during irradiation at moderate doses. However, upon exposure to large radiation doses, the enzyme loses measurable amounts of activity due to reactions with O2–• (ref. 12). It is therefore of interest to assess whether dietary agents which scavenge electrons in competition with oxygen and/or O2–• would protect mitochondria against radiation damage.

Caffeine (1,3,7-trimethylxanthine) is a component of coffee, tea and several cola-containing beverages13. Though it has been shown to have several pharmacologically useful effects, it is largely regarded as a radiosensitizer by virtue of its inhibition of DNA repair, especially as a post-treatment after UV-irradiation14,15. However, several recent studies suggest that if caffeine is present during radiation exposure, it can afford significant protection16,17. Our earlier studies have also shown that it protects against radiation-induced oxic pathway leading to seedling injury in barley18, loss of clonogenic ability in Bacillus megaterium spores19 and micronuclei induction in mice20. One recent study also showed that oral feeding of caffeine to mice protected them against radiation-induced lethality21. These studies as well as those reported earlier13,14,22 also indicate that caffeine is effective in vivo and that caffeine reaches different tissues including liver after oral feeding. It has also been shown to be metabolized by the hepatic microsomal cytochrome P-450 system23. We have shown that radioprotective action of caffeine arises from its effective scavenging of •OH, e–•aq, 1O2 (refs 16, 17, 19, 24). The present study shows that even with low concentrations, caffeine can protect the antioxidant enzyme SOD against high doses of g -irradiation as compared to two other mitochondrial enzymes which are not involved in scavenging of radicals generated during radiation such as superoxide.

end partial quote.

I wonder what the substance of choice was for the Upper Echelon of the British Nuclear Test teams.

they had a number of chemicals to choose from. I suspect Cystamine, Cysteamine and Cysteine. Plus bulk cups of tea.

“I am hale an hearty” Titterton in 1984.

http://en.wikipedia.org/wiki/Ernest_William_Titterton

Ernest William Titterton, was born of William Alfred and Elizabeth Titterton in Kettlebrook, Tamworth, UK, on 4 March 1916.

….After a call from Oliphant, who wanted to develop a small wavelength radiation generator, Titterton worked as a research officer with the British Admiralty for the early part of the second world war, working on radar systems. Though the work was classed top-secret, he was allowed to submit it to Birmingham and was awarded a PhD in physics in 1941.

After his studies in radar, Titterton decided to pursue an interest in nuclear technology and joined the British Scientific Mission in USA, which was working on the development of the first nuclear weapons. In July 1945 he was a senior member of the timing group that fired the first nuclear weapon at Alamogordo, New Mexico. A year later he was promoted to Chief Instrumentation Advisor to the Task Force Commander at the Bikini Atoll nuclear weapons testing facility. For the following year, he was Head of Electronics in the Los Alamos laboratory.
For the next three years, Titterton headed Nuclear Emulsion and Cloud Chamber Research at the Atomic Energy Research Establishment in Harwell, Oxfordshire.

In August 1950, Titterton was appointed Foundation Professor to the Chair of Nuclear Physics at the Australian National University. However, his international interests continued and he was elected a fellow of the Royal Society of Arts and Sciences of London and the American Physical Society, both in 1952. In 1954 a similar honour was bestowed upon him as one of the earliest fellows of the Australian Academy of Science.
For the next thirty years, Titterton held high positions on various science, defense and nuclear-related committees, institutes and councils in Australia, including: Australian Atomic Weapons Tests Safety Committee (1954–1956), Australian Atomic Energy Commission’s Scientific Advisory Committee (1955–1964), Council of the Institute of Defence Science, Department of Supply (1957–1972), Australian Atomic Weapons Tests Safety Committee (1957–1973), National Radiation Advisory Committee (1957–1973), Federal Government’s Defence Research and Development Policy Committee( 1958–1973), Council of the Australian Institute of Nuclear Science and Engineering (1960–1984), Council of the Australian Academy of Science (1964–1966), Advisory Committee of the Strategic and Defence Studies Centre (1967–1981)
During this time, Titterton continued to pursue his academic interests at the Australian National University, and was the Dean of the Research School of Physical Sciences, Director of the Research School of Physical Sciences (1969–1973), a professor of nuclear physics (1973–1981). He was a member of the council of Macquarie University (1978–1984).
Titterton was a strong public advocate of nuclear power for Australia.[1]
During his career, Titterton received a plethora of awards, most notably being appointed Companion of the Order of St Michael and St George, and knighthood in 1970.
[edit]Retirement

Titterton officially retired in 1981, but retained a position as a Visiting Fellow in the Department of Nuclear Physics of the Australian National University. He divorced in 1986, and was injured seriously in a car accident, which required him to use a wheelchair full-time. He died on 8 February 1990.”

A sympathetic round up of the man who claimed that the Black Mist incident belonged to the realm of myth, all the while knowing that 2 such events occurred in Australia at least and that in 1953 farmers appointed as AEC appointed radiation monitors photographed similar clouds at extreme low altitude nuclear clouds approx 180 miles from shot point in rural Downwind Nevada.

So low in altitude that Joe had to put his camera in a lead lined box which was fitted with a with a little lens aperture hole in order to get the photographs.

Titterton was the man who admitted to the Royal Commission that he could not disclose all relevant information to the members of the Atomic Weapons Safety Committee in Australia ( the committee he chaired) because he was subject to both American and British secrecy demands.

US Department of Energy Opennet Documents:

Title: LETTER TO J. FALLINI, SUBJECT: MEASUREMENT OF PERSONAL DOSAGE RECEIVED FROM RADIATION EXPOSURE DURING HARDTACK II OPERATION
Author(s): PLACAK, O.R. (* PUBLIC HEALTH SERVICE – U.S.)
Subject Terms: HARDTACK II OPERATION; PUBLIC RELATIONS; PHOTOGRAPHIC FILM DOSEMETERS; DOSE RATES; PERSONNEL MONITORING
Addressee: FALLINI J
Document Location: Location – NNSA/NSO Nuclear Testing Archive Address – P.O. Box 98521 City – Las Vegas State – NV Zip – 89193-8521 Phone – (702)794-5106 Fax – (702)794-5107 Email – CIC@NV.DOE.GOV
Document Type: CORRESPONDENCE, LETTERS, MEMOS
Publication Date: 1959 Jan 19
Declassification Status: Never
Document Pages: 0001
Accession Number: NV0152973
Originating Research Org.: PUBLIC HEALTH SERVICE
OpenNet Entry Date: 1994 Aug 27

Title: TWX TO A D STARBIRD, SUBJECT: SHASTA MR/HR AND ESTIMATED EXPOSURE TO FALLINI RANCH, RUBY HILL MINE AND EUREKA, NEVADA
Author(s): REEVES, J.E.
Subject Terms: FALLOUT; RADIATION DOSES; SHASTA EVENT; RANCHERS; PLUMBBOB OPERATION
Document Location: Location – NNSA/NSO Nuclear Testing Archive Address – P.O. Box 98521 City – Las Vegas State – NV Zip – 89193-8521 Phone – (702)794-5106 Fax – (702)794-5107 Email – CIC@NV.DOE.GOV
Document Type: CORRESPONDENCE, LETTERS, MEMOS
Publication Date: 1957 Aug 18
Declassification Status: Never
Document Pages: 0001
Accession Number: NV0017476
OpenNet Entry Date: 1994 Aug 26
Description/Abstract: NO ABSTRACT WILL BE WRITTEN FOR THIS DOCUMENT

Sorry. I need to cite these US entries. As well the following Australian ones:

“In response to the persistent reports which related the horror of the Australian Black Mist incident, in 1980 Professor Titterton, Chair of the Atomic Weapons Test Safety Committee told national radio : “No such thing can possibly occur. I don’t know of any black mists. No black mists have EVER been reported until the scare campaign was started. …If you investigate black mists sure you’re
going to get into an area where mystique is the central feature.” [20]

Blatant nuclear lie.

[20] “The British Nuclear Weapons Programme 1952 – 2002”, Editors
Douglas Holdstock and Frank Barnaby. Cross, Roger, Chapter Nine, “British
Nuclear Tests and the Indigenous People of Australia”, pp 81,
ISBN 0- 7146-8317-5,
Frank Cass & Co, London.

The Other Black Cloud
The Royal Commission paragraph 6.4.51, page 185, records the report of a
Black Cloud in 1956. It was not a ground level cloud. This report is based on a message sent “restricted priority” to the “Director Maralinga”. The message relayed Officer MacDougall’s report that “men employed at Ingomar who were camped 15 miles West of Mount Pemrhyer Bore on 27th September (1956 added in pen to the original document) report that a very Black Cloud detached itself from the main cloud and traveled Northwards and then rejoined the main cloud. ….At night when they were in bed particles of sandy dust were hitting their canvas camp sheets very similar to raindrops. Message ends. …” [7]

The Director Maralinga was William Penney. There is no record of any Health Physics response. But the report is not contested as are the reports of similar events where the reporters were not members of the British group. Perhaps Andrew Bolt could research why these things are so. Why an event reported by people approved by the British is believed, while those reports from “non approved people” are questioned to this day. By embedded profiteers who’s income is supplemented by their periodic articles repeating the 1980 Titterton Line in the 20th and 21st century gutter press.

[7] National Archives of Australia document Title: “Department of AboriginalAffairs – Atomic Weapons tests health effects.” Series Number A6456 Control Symbol R008/003 Contents Date Range: circa 1950 – circa 1985, Access Status: Open. Location: Canberra. Barcode: 4141378, Viewable online digital copy.

For sure Penney told the Safety Committe.

http://universalium.academic.ru/294833/Some_chemicals_that_exert_radioprotective_effects_in_laboratory_animals

This is not about black hats and white hats. It is about what actually occurred.

One Response to “Protection of superoxide dismutase by caffeine in rat liver mitochondria against Ý-irradiation”

  1. CaptD Says:

    I call this: Nuclear Profitganda*

    * http://www.urbandictionary.com/define.php?term=Profitganda

    Profitganda is the use of phony “feel good” information to sell an idea, product or concept to the masses.

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