Biological autoxidation. I. Decontrolled iron: an ultimate carcinogen and toxicant: an hypothesis

Our plain-English summary of Biological autoxidation. I. Decontrolled iron: an ultimate carcinogen and toxicant: an hypothesis, by S.H. Kon (Medical Hypotheses, 1978).

The study

• Author: S.H. Kon
• Journal: Medical Hypotheses
• Published: 1978;4(5):445-71
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Ionic iron at physiological pH hydrolyzes into insoluble aggregates, which disperse on slight acidification. Uncontrolled ionic iron promotes autoxidation, which crosslinks biomolecules and produces destructive activated oxygen. Defenses against autoxidative crosslinking include: 1. ferritin, the macromolecular scavenger of iron; 2. metabolic turnover, which prevents irreversible crosslinking through early catabolic degradation and replacement; and 3. enzymatic deactivation of oxygen. I am proposing that the anticrosslinking defenses are defeated by transient actions of metabolic perturbations, toxicants, oxidants and "foreign bodies", which cause oxidative crosslinking of proteins and lipids into irreversible tissue imprint: indigestible bodies containing porous limited-access spaces (LASs). The pores exclude the macromolecular ferritin and the digestive and antiautoxidation enzymes but admit ionic iron which, sheltered from ferritin, accumulates into decontrolled-iron pathogen (DIP). DIP utilizes the energy of ambient pH fluctuations to erupt from the LAS, swamp the available ferritin, poison the surroundings, catalyze autoxidation and crosslink cell components into additional LAS carriers. With time and sufficient promotion by pH fluctuations or metal-complexing agents, DIP and LAS expand. DIP injures through heavy-metal inhibition of life processes and catalysis of autoxidation. Typically, carcinogenic initiators are protein denaturants, cell poisons, "foreign bodies" and autoxidation catalysts. These are DIP-initiating properties, and DIP may be a preneoplastic stage of carcinogenesis. A DIP-model interpretation is given for the growth of asbestos bodies. DIP is an inorganic parasite. It may envelope and attack phagocytized particles.

In plain English

This was a hypothesis paper, not a study. The author offered what was called a speculative model and reported no new experiments, patients or measurements. The author proposed that iron escaping the control of ferritin, the cell's iron-storage protein, could build up inside porous, hard-to-digest debris in cells. The author called this build-up a "decontrolled-iron pathogen" (DIP) and proposed that swings in acidity release it, harming nearby cell parts through oxidation. Asbestos was used as an example of a "foreign body" that might start this process. Citing earlier work by others, the author interpreted asbestos bodies (iron-rich coats around fibers in tissue) through this model. In that interpretation, the degraded chrysotile fiber acted as a seed for a larger coat built from the body's own materials. The author also proposed that the acidity and metal-binding chemicals of tobacco smoke might explain the reported combined effect of smoking and asbestos. The author suggested this process may be a stage before cancer. The author concluded that the body's two recognized defenses could only weakly oppose it.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Theoretical hypothesis paper (Part I of a series); no original data
• Who was studied: None; no people, animals or samples were studied. The paper drew on previously published work by others.
• Exposure: Discussed theoretically: asbestos (chrysotile in particular) and other "foreign bodies" such as glass fibers, as possible starters of the proposed iron-driven process; tobacco smoke as a possible promoter
• Main results:
  • Proposal (not tested): porous, poorly digestible debris left in cells shelters iron from ferritin, so the iron escapes control and forms the proposed "decontrolled-iron pathogen"
  • Proposal (not tested): a drop in acidity level (pH) releases the accumulated iron from its shelter
  • Proposed interpretation of asbestos bodies: the original fiber acts as a seed for a larger coat built from the body's own materials, a coat that ultimately dwarfs the fiber
  • Proposal (not tested): the fluctuating acidity and metal-binding agents of tobacco smoke act as promoters of the proposed process, offered as an explanation for the reported smoking and asbestos combined effect
  • Proposal: the needle shape of asbestos fibers may account for the odd shapes of asbestos bodies, by puncturing hypothetical lipid barrier sacs
• The authors' conclusion: The authors' view was that the proposed process is likely a pre-cancer stage and has a highly destructive potential that the two recognized cell defenses can only weakly oppose. A further hypothetical defense was left to Part II.
• Limitations the authors state:
  • The author described the model as speculative
  • The author noted that no comparison of how strongly hydrous ferric oxide and ferritin bind iron was available

Topics

Medical terms in this study, explained in our Lexicon: Ferritin, Carcinogenic, Carcinogenesis, Asbestos Bodies.

Related studies

• Biological autoxidation. II. Cholesterol esters as inert barrier antioxidants. Self-assembly of porous membrane sacs. An hypothesis — S.H. Kon (1978)
• Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells — C.C. Chao, S.H. Park, et al. (1996)
• Free radical generation at the solid/liquid interface in iron containing minerals — B. Fubini, L. Mollo, et al. (1995)
• Regulation of priority carcinogens and reproductive or developmental toxicants — K. Hooper, J. LaDou, et al. (1992)
• The biological effect of asbestos exposure is dependent on changes in iron homeostasis — A.J. Ghio, J.M. Soukup, et al. (2016)
• Some biological properties of respirable iron ore dust — D. Keast, N.P. Sheppard, et al. (1987)

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