Human liver cancer does not have the same ESR signal as normal liver. [1]
Samples of liver normally have a very prominent ESR, which is undetected in cancerous liver samples. Mallard and Kent compared normal rats with rats treated with the carcinogen butter yellow. Figure 1 below shows that normal liver tissue has an ESR peak, which is absent from chemically-induced liver cancer. The signal intensity is proportional to the number of unpaired electrons sensed by the instrument, thus the authors concluded that free radicals were absent from rat cancer. [2]
The insoluble protein fraction of rat liver carcinoma, which contributes a significant portion of the signal, lacked a detectable ESR signal, shown in Figure 5 below. The absence of ESR signal in cancerous tissue could be related to faulty cytoskeletal proteins, such as tubulin.
Szent-Gyorgyi gave the explanation that cancerous proteins lack the normal ESR signal because malignant proteins have paired electrons that fill the available molecular energy levels, and not enough unpaired electrons. He put forth an elaborate history for the living state and cancer. [3,4]
In the period before aerobic life, Szent-Gyorgyi presumed that the atmosphere would be strongly reducing, dominated by electron donors, that is, molecules would tend rather to give off than take up electrons. During pre-aerobic times, proteins contained full orbitals, occupied mostly by electron pairs. This situation still persists in the plant kingdom, where plants are mostly involved with chemical processes of reduction, not oxidation. In plants and during pre-aerobic times, there would be little electronic mobility between one molecule and the next, because filled orbitals tend to have a low reactivity with other electron pairs that are held strongly in place. Szent-Gyorgyi speculated that primitive cells would be unable to develop charge-transfer reactions between neighboring proteins, because few proteins could enter the radical state. Then he imagined the appearance of oxidative chemical processes. Oxygen, an electron acceptor, began the second aerobic phase of life's existence. Free radicals such as oxygen contain an uncoupled electron (radicals), and radicals are known for their great reactivity. Szent-Gyorgyi wrote:
References
1. COMMONER, B. and J.L. TERNBERG 1961. Free radicals in surviving tissues. Proc. Natl. Acad. Sci. U. S. A. 47, 1374-1384. DOI:10.1073/pnas.47.9.1374
2. MALLARD, J. R. and J. KENT 1964. Differences observed between electron spin resonance signals from surviving tumour tissues and from their corresponding normal tissues. Nature. 204, 1192. DOI:10.1038/2041192a0
3. Szent-Gyorgyi, A. 1977. The living state and cancer. Proc. Natl. Acad. Sci. U. S. A. 74, 2844-2847. DOI:10.1073/pnas.74.7.2844
4. Pohl, H. A., P.R. Gascoyne and A. Szent-Gyorgyi 1977. Electron spin resonance absorption of tissue constituents. Proc. Natl. Acad. Sci. U. S. A. 74, 1558-1560. DOI:10.1073/pnas.74.4.1558
Samples of liver normally have a very prominent ESR, which is undetected in cancerous liver samples. Mallard and Kent compared normal rats with rats treated with the carcinogen butter yellow. Figure 1 below shows that normal liver tissue has an ESR peak, which is absent from chemically-induced liver cancer. The signal intensity is proportional to the number of unpaired electrons sensed by the instrument, thus the authors concluded that free radicals were absent from rat cancer. [2]
The insoluble protein fraction of rat liver carcinoma, which contributes a significant portion of the signal, lacked a detectable ESR signal, shown in Figure 5 below. The absence of ESR signal in cancerous tissue could be related to faulty cytoskeletal proteins, such as tubulin.
Szent-Gyorgyi gave the explanation that cancerous proteins lack the normal ESR signal because malignant proteins have paired electrons that fill the available molecular energy levels, and not enough unpaired electrons. He put forth an elaborate history for the living state and cancer. [3,4]
In the period before aerobic life, Szent-Gyorgyi presumed that the atmosphere would be strongly reducing, dominated by electron donors, that is, molecules would tend rather to give off than take up electrons. During pre-aerobic times, proteins contained full orbitals, occupied mostly by electron pairs. This situation still persists in the plant kingdom, where plants are mostly involved with chemical processes of reduction, not oxidation. In plants and during pre-aerobic times, there would be little electronic mobility between one molecule and the next, because filled orbitals tend to have a low reactivity with other electron pairs that are held strongly in place. Szent-Gyorgyi speculated that primitive cells would be unable to develop charge-transfer reactions between neighboring proteins, because few proteins could enter the radical state. Then he imagined the appearance of oxidative chemical processes. Oxygen, an electron acceptor, began the second aerobic phase of life's existence. Free radicals such as oxygen contain an uncoupled electron (radicals), and radicals are known for their great reactivity. Szent-Gyorgyi wrote:
"The appearance of oxygen meant the appearance of an electron acceptor capable of taking up single electrons and in so doing separating electrons of electron pairs, leading to the production of unpaired electrons, electron holes, and partially occupied orbitals. This lent a high and subtle reactivity to proteins, generating the unbalanced forces capable of linking molecules together to form integrated functional structures." [4]When Szent-Gyorgyi and colleagues failed to detect free radicals in cancer tissue, they predicted that cancer therapies one day might aim to restore free radical content.
References
1. COMMONER, B. and J.L. TERNBERG 1961. Free radicals in surviving tissues. Proc. Natl. Acad. Sci. U. S. A. 47, 1374-1384. DOI:10.1073/pnas.47.9.1374
2. MALLARD, J. R. and J. KENT 1964. Differences observed between electron spin resonance signals from surviving tumour tissues and from their corresponding normal tissues. Nature. 204, 1192. DOI:10.1038/2041192a0
3. Szent-Gyorgyi, A. 1977. The living state and cancer. Proc. Natl. Acad. Sci. U. S. A. 74, 2844-2847. DOI:10.1073/pnas.74.7.2844
4. Pohl, H. A., P.R. Gascoyne and A. Szent-Gyorgyi 1977. Electron spin resonance absorption of tissue constituents. Proc. Natl. Acad. Sci. U. S. A. 74, 1558-1560. DOI:10.1073/pnas.74.4.1558
