Thursday, June 7, 2012

Yet another similarity between A new model of Carcinogenesis and the processes used to describe metal induced interacelluar effects

Food for thought:

Excertps from Metal on metal hip resurfacing arthroplasty; Oxford University; Acta Orthopaedica 2008.

Reactions with metal ions can lead to generation of free radicals:  reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can in turn cause cellular dysfunctions.  Inside the cells, Cr6 is oxidized to cr3 in a series of steps to generate free radicals......Free radicals catalyze the oxidation of protein and phospholipids (a process known as lipid peroxidation.)...Permanent modification of genetic material resulting from this "oxidative damage" represents the first step in mutagensis, carcinogensis and ageing.  Although no evidence has been found for direct binding of Co to DNA, direct binding of Cr3 to DNA is well documented (Wolf et al. 1989).  In cells, 2 main processes exist to correct DNA aberrations to restore the integrity of the genome:  BER and NER.  Under stimulation by Co2 and Cr6, both of these repair mechanisms are inhibited. [added by Connie/when you have revision surgery, these processes come into play.]

Now lets look at The view of a new model of Carcinogenesis

excerpts from  Molecular Medicine  2012 Mar-Apr;16(3-4); 144-153

....According to this new model, the development of any cancer requires that the future tumor cell both acquires a complex set of DNA alterations and develops an alteration in the metabolism of O2.  It is widely acknowledged that the altered genome of tumor cells plays a key role in carcinogenesis.  Evidence suggest that an alteration in the metabolism of O2 from the pathway generates energy to the pathway that produces ROS (reactive oxygen species) may also play an important role in the development of cancer......Most carcinogenic agents have been shown to induce DNA alterations.  Most carcinogenic agents also induce oxidative stress....Most chemical carcinogens need to be enzymatically activated to become genotoxic......

Targeting the Altered Oxygen metabolism of tumor cells for the treatment of cancer

Cancer cells have an alteration in the metabolism of O2 which results in increased glycolytic activity.  the high glycolytic  activity of cancer cells is essential yo their survival. The O2 metabolism of cancer cells can be exploited to kill cancer less selectively by increasing the cellular levels of H2O2and or by attenuating glucolysis.  These effects could be achieved by the use of peroxidant agents and glycolysis inhibitors, alone or in combination.

The role of ROS in the activity of may anticancer agents is increasingly  being acknowledged and induction of oxidative stress by peroxidant agents is emerging as an attractive anticancer strategy.

All just completely fascinating isn't it?  all of this stuff is connected.  I wish I would have taken some molecular biology,  immunology and biochemistry courses in lieu of piano lessons!

One more item:

The role of oxidative stress in carcinogenesis.


Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.


Chemical carcinogenesis follows a multistep process involving both mutation and increased cell proliferation. Oxidative stress can occur through overproduction of reactive oxygen and nitrogen species through either endogenous or exogenous insults. Important to carcinogenesis, the unregulated or prolonged production of cellular oxidants has been linked to mutation (induced by oxidant-induced DNA damage), as well as modification of gene expression. In particular, signal transduction pathways, including AP-1 and NFkappaB, are known to be activated by reactive oxygen species, and they lead to the transcription of genes involved in cell growth regulatory pathways. This review examines the evidence of cellular oxidants' involvement in the carcinogenesis process, and focuses on the mechanisms for production, cellular damage produced, and the role of signaling cascades by reactive oxygen species

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