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Oxidative Stress as a Precursor and Mechanism for Carcinogenicity

IARC and others (Smith et al) have identified 10 key characteristics which may be used/considered in the evaluation of carcinogenicity, one of which is oxidative stress.  How strong or compelling, if at all, would the data need to be for considering OS as a putative  and defensible MOA for carcinogenicity, or would there need to be other tangential/correlative data (e.g., tumors) available.  In other words, is OS sufficient by itself as an indicator and compelling basis for a carcinogenic concern? 
1
K. Kannan
No, OS is a global marker of stress and is not specific to exposure to chemicals or chemical classes.  Dietary factors can affect oxidative stress levels as well.  Many disease conditions can affect oxidative stress.  Therefore oxidative stress markers alone cannot predict carcinogenicity.
1
Serkan YILMAZ
Carcinogenesis is multistep process and OS is not sufficient by itself as an indicator and compelling basis for a carcinogenic concern
0
Singh Z
Oxidative stress (OS) can be a key factor responsible for many disease pathologies. MDA estimations or similar compound elevations may be associated with different disease conditions. But, OS cannot be directly and absolutely taken as an indicator and compelling basis for cancer concern. 
1
Maria Dagli
 Indirectly YES, because "Oxidative stress is viewed as an imbalance between the production of reactive oxygen species (ROS) and their elimination by protective mechanisms, which can lead to chronic inflammation.". "A substantial body of evidence supports the conclusion that chronic inflammation can predispose an individual to cancer, as demonstrated by the association between chronic inflammatory bowel diseases and the increased risk of colon carcinoma. Chronic inflammation is caused by a variety of factors, including bacterial, viral, and parasitic infections, chemical irritants, and nondigestible particles. The longer the inflammation persists, the higher the risk of associated carcinogenesis". Tumor promoting inflammation has been classified as an enabling characteristic in Hanahan and Weinberg's  "Hallmarks of Cancer: the Next Generation" (DOI:https://doi.org/10.1016/j.cell.2011.02.013). 
I understand that if a compound increases oxidative stress, this must cause chronic inflammation and may lead to cancer. Of course, risk/safety assessments can be performed to detect the most suitable dose for the compound, that does not lead to chronic inflammation. 
0
mkgoodness
Yes, we described in details that loss of balance in tumoricidal and tumorigenic properties of effective immunity (Yin-Yang of immune surveillance) were described to be involved in growth promoting and anabolic properties of immune system in multistep tumorigenesis and angiogenesis.  The following recent articles are extension of Khatami et al accidental discoveries on the role of inflammation in experimental models of acute and chronic inflammatory diseases. The results describe a series of first evidence on direct role of inflammation-induced time-course kinetics of immune dysfunction in multistep tumorigenesis and angiogenesis.
 
https://doi.org/10.1002/ctm2.215

4th book: Khatami M: In Inflammation, Aging and Cancer: Biological Injustices to Molecular Village that Guard Health. Berlin: Springer; 2017: 1‐ 389. http://www.springer.com/gp/book/9783319664736 

Unresolved inflammation: ‘immune tsunami’ or erosion of integrity in immune‐privileged and immune‐responsive tissues and acute and chronic inflammatory diseases or cancer. Exp Opin Biol Ther. 2011; 11: 1419‐ 1432

Chronic inflammation: synergistic interactions of recruiting macrophages (TAMs) eosinophils (Eos) with host mast cells (MCs) and tumorigenesis in CALTs. MCSF, suitable biomarker for cancer diagnosis! Cancers. 2014; 6: 297‐ 322. 

“Yin and Yang” in inflammation: duality in innate immune cell function and tumorigenesis. Exp Opin Biol Ther. 2008; 8: 1461‐ 1472.

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Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases. Cell Biochem Biophys. 2009; 55: 55‐ 79.

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0
W. Foster
Not at all. Oxidative stress (OS) is general marker of cell or tissue stress; however, enzymatic pathways are unregulated in response to OS obviating any adverse outcome. Moreover, OS is not specific to chemicals or to any chemical exposure or class of chemicals. Evidence of oxidative stress is present within the electron transport chain, in cells during steroidogenesis and is multiple disease conditions. Therefore, in my opinion, on its own evidence of oxidative stress cannot predict carcinogenicity. It must be accompanied by other indicators. 
0
Muhammad Ayaz
Free radicals are frequently generated from endogenous as well as exogenous aerobic metabolism. These free radicals are normally neutralized by human immune system antioxidant system including catalase, hydroperoxidases and glutathione. In situation where these free radicals are liberated in excessive amount of the immune system is compromised then these free radicals initiate chain reactions thus damaging cells, nuclear materials, proteins, lipids and accelerate inflammatory disorders. These radicals attack DNA thus causing mutations as well as breakage of DNA strands. Changes in the genetic materials leads to excessive tumor growth as a result of loss of control on cell cycle arrest. These free radicals also act as signaling molecules and participate in regulation of cells signaling processes. The process of mutagenesis via free radicals induced DNA damage is well established and evidences indicate that free radicals are implicated in the expansion of tumor clones as well as acquirement of malignant characteristics. Subsequently, free radicals are considered as a vital group of carcinogens 

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