Melanoma (Skin Cancer): Causes and Treatment

To trace the path of free radicals in inducing skin cancer


Cause of cancer

“The major cause of any cancer is a mutation, or change, in the DNA of a particular cell. In the case of melanoma, the cell is the melanocyte....Many scientists now believe that ultraviolet A rays (of the sun) may cause melanoma at worst and premature aging of the skin at best” (Kaufman, H. The Melanoma Book. 2005:26-27, parenthetical mine).

Role of free radicals in melanoma

The main aim is to verify that free radicals cause cancer. Then toward the end, to treat melanoma with immunotherapy - using interleukin-2. Given that there are volunteers for this trial.

Let’s trace how free radicals induce melanoma or skin cancer. There are two kinds of free radicals that can readily induce melanoma: singlet oxygen and hydroxyl radical.

Singlet oxygen

Expose the skin to a heat energy of more than 1216 kcal/mol with the use of ultraviolet rays. This energy is enough to excite at least one unpaired electron of molecular oxygen, indicated as O22-. Molecular oxygen has two unpaired electrons in the outermost orbital that are spinning around the whole molecule in parallel direction. (An orbital is the path of electrons around the nucleus of an atom.) When excited, one unpaired electron reverses its spin. Now the two unpaired electrons spin in opposite directions (Prasad, M.N. Heavy Metal Stress in Plants. 1999:103). A singlet oxygen consists of two oxygen atoms with two unpaired electrons spinning in opposite directions around the whole molecule. Singlet oxygen is a free radical. Others consider it as a reactive oxygen species (ROS). I prefer to consider it as a free radical. Anyway, even if it is a ROS, it also acts like a free radical in that each of the unpaired electrons grabs an electron of other molecules and cause injury. Thus the melanocyte of the skin whose molecule had been grabbed of electron is injured. Its DNA mutates and shows as tumor that graduates into a melanoma. Singlet oxygen can grab two electrons from melanocytes simultaneously owing to the opposite directions of the spin of unpaired electrons. Thus it is more dangerous than molecular oxygen.

Hydroxyl radical

Another free radical that can be formed by ultraviolet rays is hydroxyl radical. Water in the skin hit by UV rays is excited and forms H2O+ (Brown, et al. Chemistry the Central Science. 7th edition. 1975). Note that plus sign which indicates an electron ejected from the orbital. H2O+ reacts with another water molecule and forms water and hydroxyl radical, indicated as OH•. Note that dot as superscript. Hydroxyl radical is different from hydroxyl, indicated as OH-, (with a negative superscript) which is an ion from a water that had been dissociated into hydrogen and hydroxyl; it has to do with acidity of a fluid. Hydroxyl radical is the most destructive free radical (Sharma, H. Freedom from Disease. 1993). It grabs electrons from melanocytes of the skin and causes mutation of DNA that shows as tumor or cancer.

Basal cell carcinoma is the most common skin cancer formed in the sun-exposed skin. Either the hydroxyl radical or singlet oxygen will induce basal cell carcinoma. It is not relevant to distinguish which of them causes melanoma in this trial. Besides, either of them is formed by ultraviolet rays; or both of them are formed.

From mutation to cancer

Injury in DNA consists in the break up of hydrogen bonds that abound in the chromosome. The hydrogen bond is the easiest to break because it is only 5% as strong as that of the other bonds like ionic bond and covalent bond. It is the electron of the hydrogen atom that is grabbed by free radicals. Once its electron is taken away, the hydrogen atom dies, as it were, because it is composed of one electron and one proton only; no way to reconstruct itself. It is like a chain that is broken when one or two links had been broken earlier. The damage shows as deletion, break, thickening, shortening of chromosomes. (A cell contains 46 chromosomes). A cell that sustain such damage is abnormal.

Free radicals also destroy the p53 gene in the cell. This is a suppressor gene that stops cell division of mitotic cells. (The cells of the body are mitotic; that of "seed" of man or egg of woman are meiotic.) Once also mutated p53 gene cannot stop the cell where it resides from dividing. A normal p53 gene can stop the cell cycle in two checkpoints in the interphase: one at transition between G1 to S and at another checkpoint at transition between G2 and M (mitosis). Once mitosis has started, tumor or cancer develops (Cummings, M. Human Heredity, Principles and Issues. 2009). That is why a mutated cell keeps on dividing, that means uncontrolled growth. That's what a tumor or cancer is, its growth is uncontrolled. Tumor or cancer starts in one mitotic cell only then go on to divide into two, into four, into 16, into 32 and so forth and so on. When the population of abnormal cells breach the matrix that confines them, they escape and invade neighboring cells. The bottom of the matrix is the first to give up, dissolved by protease or bromelain that is also found in pineapple and papaya. Once they reach blood or lymph fluid the cancer cells swim along, as it were, and reach other parts of the body and start colonies there. Melanoma can reach the brain.

Meantime no antioxidants

Melanoma can be countered with antioxidants. That is why during this trial volunteers should not take antioxidants, most especially carrots. This food, or vitamin A, is the only antidote of singlet oxygen. It absorbs heat that dissipates the heat energy applied to produce singlet oxygen. Carrot contains carotene that absorbs heat much like chlorophyll absorbs heat that converts carbon dioxide into food for plants.

Antioxidants also counter hydroxyl radical by donating the electrons that it needs to stabilize. Supplemented antioxidants are vitamin A, C, E, coenzyme Q10, and B-complex. Enzyme antioxidants built-in in the body are superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione synthase, and catalase. Melatonin is also an antioxidant whose precursors are tryptophan and serotonin that are found in fruits and cereals. Antioxidants, "may help prevent skin damage" (Kaufman, page 46) especially vitamin E for the skin.

If the built-in antioxidants of the volunteers in this trial are abundant it is probable that they will not grow a mole of melanoma.

Of course, volunteers should not apply sunscreens, with sun protection factor (SPF), that work by "reflecting, absorbing, or scattering the ultraviolet A and B rays so that they cannot penetrate into the skin" (Kaufman, page 45).

Symptom of melanoma

In the area of the skin exposed to UV rays shows up a mole that is reddish. Moles can grow somewhere else in the body. If in time the size of this mole increases, then it is melanoma that might be benign. We will allow that benign melanoma to grow up to Stage I cancer only so that treatment is ensured.

“Cancers that are more aggressive in their growth and can spread to other parts of the body are called malignant. Cancers that remain small in size and do not spread are called benign, and generally behave in a less threatening manner” (Kaufman, page 9).

“Stage I includes those melanomas that are less than one millimeter thick and those that are one-two millimeters thick without ulcerations” (Kaufman, page 93).

Treatment

The treatment of skin cancer is already advanced, unlike other kinds of cancer. There are over 200 kinds of cancer.

To diagnose for Stage I melanoma there is no need for imaging technology like X-ray, no need for blood test. Routine skin examination will do. One exception is when the patient has headache in which case magnetic resonance imaging (MRI) might be used on the head to see if melanoma had metastasized to the brain.

Biopsy will help. It confirms the diagnosis and shows how deep the melanoma is. Biopsy may remove a small mole but it is not an adequate treatment, according to Dr. Kaufman.

Sometimes, a blood test may be needed to ensure against bleeding. Some persons may have inadequate platelets that prevent profuse bleeding. If you have other medical problems an X-ray and electrocardiogram (ECG) will help.

“The treatment of primary melanoma (Stage I and II) is surgical excision or removal of all melanoma cells in order to halt its spread” (Kaufman, page 107).

Immunotherapy (interleukin-2) is the treatment preferred for metastatic melanoma. It targets the cancer cells and kills the cancer cells only leaving the healthy cells in the vicinity unharmed, according to Kaufman. It is unlike chemotherapy that produces a lot of free radicals that kill both cancer cells and healthy cells in the vicinity. In addition, chemotherapy destroys the bone morrow (maker of blood), kills blood cells, and leaves the patient weak. Chemo also kills hair cells that is why hair loss is a side effect.

"We now believe that the immune system can recognize and destroy cancer cells in a similar manner to the way the immune system fights infection...

"To date the most effective immunotherapy for melanoma and kidney cancer has been interleukin-2.... It is a cytokine that promotes the survival, growth, and killer functions of T cells" (Kaufman, page 154). T cells are components of the immune system that develop in the thymus gland. In some patients interleukin-2 can kill all melanoma.

We have demonstrated how free radicals like singlet oxygen and hydroxyl radical cause melanoma. We have discussed how antioxidants prevent melanoma. Also we have demonstrated how biopsy and immunotherapy treat melanoma.

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