Non-enzymatic extramicrosomal bioactivation of chemical carcinogens by phagocytes: a proposed new pathway

Our plain-English summary of Non-enzymatic extramicrosomal bioactivation of chemical carcinogens by phagocytes: a proposed new pathway, by A.A. Roman-Franco (Journal of Theoretical Biology, 1982).

The study

• Author: A.A. Roman-Franco
• Journal: Journal of Theoretical Biology
• Published: 1982;97(4):543-55
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A theory of bioactivation of precarcinogens is presented whose new features are the following: (1) it proposes a non-enzymatic pathway for bioactivation, (2) it explains the role of inert substances in carcinogenesis, (3) it explains the synergism between inert substances and chemical carcinogens in the genesis of neoplasms and (4) it explains the role of inflammation in carcinogenesis. The theory proposes that during the attempted phagocytosis of fibrous minerals, selected foreign bodies and analogous substances, production of reactive oxygen products takes place. These products are released from phagocytic cells, and can have several fates: (1) they can react with each other to yield even more strongly reactive species, (2) they can react with unsaturated molecules yielding mutagenic substances or (3) they can do both. When such species interact either with polynuclear aromatic hydrocarbons or unsaturated fatty acids, products capable of initiating a neoplastic transformation are formed. In this manner we explain, for example, the synergism between cigarette smoking and asbestos in causing a high incidence of cancer of the lung among exposed subjects. This particular example is prototypic for the whole field of “foreign body” or “solid state” carcinogenesis. That extramicrosomal bioactivation does occur in the biological setting is proposed here as complementary to the classical mono-oxygenases-mediated bioactivation processes.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

In plain English

This article was a theoretical paper, not an experiment or a study of people. Drawing on earlier research by others, the author proposed a new way that chemicals could be turned into cancer-causing forms in the body. The theory proposed that when phagocytes (scavenger cells) try to engulf fibrous minerals such as asbestos, certain foreign bodies and similar substances, they produce reactive forms of oxygen. These products, acting outside the usual enzyme systems, could react with polynuclear aromatic hydrocarbons or with unsaturated fatty acids to form products capable of starting cancer. The author suggested calling substances that act this way "proinitiators" and offered the pathway as a possible addition to the classic enzyme routes. The author concluded that the hypothesis explains the cocarcinogenicity of asbestos fibres in the airways, where cigarette-derived precarcinogens are present, and the combined effect of smoking and asbestos on lung cancer. In the pleura, the author proposed that polyunsaturated fatty acids (PUFAs) are the putative precarcinogen. The author noted that how hydroxyl radicals form in this setting was still under debate. No new data were reported.

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 paper (hypothesis based on published literature); no original data
• Exposure: Attempted phagocytosis of fibrous minerals (asbestos given as the prime example), selected foreign bodies and analogous substances, together with precarcinogens such as polynuclear aromatic hydrocarbons (e.g. from cigarette smoke) and unsaturated fatty acids
• Main results:
  • Proposed (not tested): reactive oxygen species released by phagocytes react with polynuclear aromatic hydrocarbons or unsaturated fatty acids to form products capable of initiating cancer
  • The author offered the theory as an explanation for the synergism between cigarette smoking and asbestos in lung cancer among exposed subjects
  • The author proposed that substances acting this way be called proinitiators
  • The proposed pathway was presented as an alternative that may add to the classic monooxygenase (enzyme) routes
  • In the pleura, the author proposed that polyunsaturated fatty acids (PUFAs) are the putative precarcinogen
• The authors' conclusion: The author concluded that the hypothesis explains the cocarcinogenicity of asbestos fibres in the bronchial environment, where cigarette-derived precarcinogens are available, and in the pleura, where the author proposed that polyunsaturated fatty acids are the putative precarcinogen
• Limitations the authors state:
  • The author stated that the mechanism by which hydroxyl radical is generated in phagocytes was still under debate

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Neoplasm, Inflammation, Phagocytosis.

Related studies

• Asbestos induces selective release of lysosomal enzymes from mononuclear phagocytes — P. Davies, A.C. Allison, et al. (1974)
• Human mononuclear phagocytes express the insulin-like growth factor-II/mannose-6-phosphate receptor — W.N. Rom (1991)
• A synergistic interaction between Bacillus Calmette-Guérin (BCG) and NADPH oxidase stimulants on the production of reactive oxygen metabolites by human mononuclear phagocytes — P.W. Nyberg, S.A. Nordman, et al. (1994)
• Transport of a carcinogen, benzo[a]pyrene, from particulates to lipid bilayers: a model for the fate of particle-adsorbed polynuclear aromatic hydrocarbons which are retained in the lungs — J.R. Lakowicz, D.R. Bevan, et al. (1980)
• War on Carcinogens: industry disputes human relevance of chemicals causing cancer in laboratory animals based on unproven hypotheses, using kidney tumors as an example — R.L. Melnick, J.M. Ward, et al. (2013)
• Cytochrome P450-mediated pulmonary metabolism of carcinogens: regulation and cross-talk in lung carcinogenesis — S. Anttila, H. Raunio, et al. (2011)

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