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Know Cancer (3 of 3)

The following key self-defense mechanisms have all been suppressed, bypassed or somehow beaten when cancer gets underway.



DNA Repair

Recall from the previous page that one of the main enabling mechanisms for cancer causation is genetic instability caused by external agents. For example, UV-ray radiation from the sun, X-ray radiation, certain pesticides, some industrial chemicals, and even a number of chemicals found in certain foods (e.g. french fries, barbecued meats) can cause this sort of damage. However, every cell in the body has a number of very elaborate repair mechanisms that can be deployed to fix this sort of damage when it occurs. So normally, these sorts of exposures don’t result in cancer.

Yet in situations where cancer develops, these repair mechanisms have been overwhelmed. This can happen if the cells that are damaged have been exposed to disruptive chemicals that inhibit or suppress proper DNA repair function (e.g., EDTA). It can also result if the genetic damage that is done to the cell actually damages the DNA repair machinery. Also if damage that occurs is extensive, the DNA repair systems may simply not be robust enough to make all necessary repairs.

Inflammation Suppression

Also recall from the previous page that another important enabling mechanism involved in many cancers is chronic inflammation. Chronic inflammation can occur at sites where persistent infections have occurred, and when the immune system has not cleared that infection. It can also occur if the hypothalamic-pituitary-adrenal axis (i.e., stress-axis) has been disrupted and is either producing too much cortisol or too little cortisol.

Cortisol is the main output of the adrenal gland and it is used to make bodily cortisone. The stress axis can use cortisol production to both instigate inflammation (via low levels of cortisol production), and suppress inflammation (via higher levels of cortisol production) by interacting with a master-inflammatory chemical messenger called Macrophage Migration Inhibitory Factor (MIF). Low levels of cortisol instigate MIF which is then able to instigate an entire inflammatory cascade, while high levels of cortisol can suppress the action of MIF. So if the stress axis has been disrupted and higher levels of cortisol are not available when needed, it can result in an outcome that is permissive of chronic inflammation.

Unfortunately, there are virtually no regulations at all that focus on the possibility that the cumulative effects of disruptive chemical agents may be damaging adrenal function, and there hasn't been any emphasis on disruptive agents that might impair the proper functioning of the stress-axis, even though it has a crucial role to play in the management of chronic inflammation. Also, there hasn't been any focus placed on the disruption of MIF, even though it plays an important role in proper immune system function, and even though it has been shown to be a key mediator in a long list of inflammatory diseases, and squarely implicated in cancer.

Anti-Growth Signalling

Another key mechanism that is supposed to help prevent unwarranted cellular proliferation is anti-growth signalling. At any given point in time, it may be important for the cell not to grow, divide and replicate, so all cells have machinery that is supposed to prevent this from happening at inopportune times.

For example, to maintain genome stability, cells with damaged DNA must ensure that cellular growth is arrested while DNA repair is taking place. The retinoblastoma tumor suppressor protein (referred to as pRb) is best known for its role in this important function, but this key protein is frequently inactivated in human cancers.

This sort of inactivation of pRb can occur when DNA is damaged. However it can also occur when it is disrupted by certain chemicals. For example, a number of notoriously carcinogenic pesticides (e.g., heptachlor, chlordane, and toxaphene) specifically disrupt pRb function. Again, there are no regulatory initiatives in place in most countries to prevent this critical mechanism from being disrupted by commonly encountered chemicals.

Programmed Cell Death (Apoptosis)

Apoptosis, or programmed cell death, is another key defensive mechanism. It is a highly regulated form of cell death that plays a pivotal role in the elimination of unwanted, damaged, or infected cells. Normally apoptosis can be triggered externally by the cells death receptor (DR) or it can be enabled by internal pathways. Either way, this important capability should stop damaged cells from proliferating (e.g., if DNA repair has been overwhelmed), but this key line of defense is not functioning properly in cancer.

A number of important pieces of cellular machinery combine to make this mechanism work. For example, apoptosis induced by the p53 protein is firmly established as a central mechanism of tumor suppression. So damage to DNA can result in mutations of p53, and other important regulators of apoptosis can disrupt this capability. But this function can also be disrupted by specific chemicals as well. For example, the pesticides parathion-ethyl and malathion have both been shown to cause mutations that affect p53 function. Again, there are no regulatory initiatives in place in most countries to prevent this critical mechanism from being disrupted by commonly encountered chemicals.

Replication Limit (Senescence)

Another important safeguard mechanism that should stop proliferating cells from becoming immortalized is a practical limit that has been established within all cells to prevent endless replication. A structure on the end of the chromosomes called a telomere is reduced in length each time a cell makes a copy of itself, and when the telomere is shortened to a critical length, a process called replicative senescence forces the cell into a state of permanent growth arrest. So senescence is yet another important tumor suppressor that should prevent the proliferation of seriously damaged cells

However, the immortalized cells that are proliferating in cancer have found a way to bypass this mechanism as well. This mechanism can be rendered dysfunctional when DNA is damaged, but it can also be manipulated chemically. For example, elevated levels of an enzyme called telomerase can extend the length of telomeres on the chromosomes, which can delay senescence, and allow cellular proliferation to continue when it would otherwise be stopped. And one chemical that can elevate levels of this enzyme is arsenic (a known carcinogenic). Once more, there are no regulatory initiatives in place in most countries to ensure that this critical mechanism is not disrupted

The Immune System

Finally, the last line of defense which should normally prevent tumors from forming is the immune system. It consists of a great number of important cell types that can suppress proliferating cells that are forming tumors. For example, T-cells, Natural Killer cells, macrophages and dendritic cells all have an important role to play in tumor eradication. Yet in cancer the immune system is not effective in this task.

In some instances, certain kinds of DNA damage can disrupt the cellular machinery within the cell that is supposed to be used to signal for help if all other lines of defense have failed. However, this is another area where disruptive chemicals can play havoc with our own cancer defense mechanisms. Indeed, a great number of registered pesticides that are in widespread use have been shown to have disruptive (i.e., immunosuppressive) potential. Unfortunately, in most countries these chemicals are screened individually and only assessed for immune system toxicity. The cumulative effect that all of these chemicals have on the immune system, and the extent to which these exposures play a role in suppressing proper immune function is simply not known. And again, unfortunately there are no regulatory initiatives in place to ensure that this critical, and last line of defense against cancer is not being materially disrupted by commonly encountered chemicals.

Cancer Self-Defense

It should be obvious from this review of all of the known defense mechanisms that should stop cancer from ever starting, that a properly working set of defenses is crucial for cancer avoidance. For example, these defenses are so effective when they are working properly that a surprising percentage of people who are routinely exposed to carcinogens still don’t get cancer (e.g., chronic smokers).

Obviously, avoiding exposures to known carcinogens would be a top priority in any pro-active cancer prevention program. But what about exposures to non-carcinogenic chemicals that have the disruptive ability to very selectively weaken or disable the many cancer self-defense mechanisms that have been identified above? Shouldn’t we be equally vigilant in our efforts to ensure the public avoids disruptive exposures to individual chemicals that can weaken these defenses as well (i.e., even if none of those chemicals are carcinogenic on their own)?

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