Chemistry of Cancer Dr. Maher Atteya. Free Radicals are very reactive species (chemicals) They have unpaired single electron in the outermost orbit.

Chemistry of Cancer

Dr. Maher Atteya

Free Radicals are very reactive species (chemicals)

They have unpaired single electron in the outermost orbit

This unstable configuration leads to energy released to adjacent molecules

The free radicals damaging the biological systems are called “reactive oxygen species”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684512/

Free Radicals

http://chemistry2.csudh.edu/rpendarvis/Radicals.html

Free Radical Chemistry Examples

Reactive oxygen species are formed by:

1. UV or X ray or gamma radiations

2. Metal catalyzed reaction in the human body

3. Pollution

4. Neutrophils and macrophages during inflammation

Cadenas E. Biochemistry of oxygen toxicity. Ann Rev Biochem. 1989;58:79–110

Reactive Oxygen Species

Macrophages (Greek: big eaters, from makros "large" + phagein "eat"; abbr. MΦ) are cells produced by the differentiation of monocytes in tissues. Human macrophages are about 21 micrometres (0.00083 in) in diameter.[1] Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense (innate immunity) as well as help initiate specific defense mechanisms (adaptive immunity) of vertebrate animals. Their role is to phagocytose (engulf and then digest) cellular debris and pathogens, either as stationary or as mobile cells.

http://en.wikipedia.org/wiki/Macrophage

Neutrophil: A type of white blood cell, a granulocyte that is filled with microscopic granules, little sacs containing enzymes that digest microorganisms. Also known as polymorphonuclear leukocyte.

http://www.paolobellavite.it/neutrophil.html

5. Some other resources often missed are: cigarette smoke, herbicides, high fats, pesticides,

smog, car exhaust, certain prescription drugs, rancid foods, alcohol, some of food and water supplies, stress and unhealthy diet etc…

http://vitanetonline.com/library/Free-Radicals-and-Cancer/

Two Resources:

1. Endogenous Resources:Mitochondria, cytochrome P450 metabolism, peroxisomes, and inflammatory cell activation

Inoue M, Sato EF, Nishikawa M, et al. Mitochondrial generation of reactive oxygen species and its role in aerobic life. Curr Med Chem. 2003;10:2495–505

Free Radicals Sources

“Mitochondria is considered the powerhouse for cell activity and provides the energy needed for the cell to break down glucose and other food molecules. The mitochondria is a unique structure within the cell made up of folded internal membranes that contain proteins and enzymes that carry our cell respiration. The end product of this whole process is the production of molecules of adenosine tri-phosphate (ATP) which is used where ever the cell needs energy.”

http://answers.ask.com/Health/Diseases/what_is_a_mitochondria

“The cytochrome P450 superfamily (officially abbreviated as CYP) is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances such as drugs and other toxic chemicals. CYPs are the major enzymes involved in drug metabolism and bioactivation, accounting for about 75% of the total number of different metabolic reactions.”

http://en.wikipedia.org/wiki/Cytochrome_P450

2. Exogenous Resources:

Xenobiotics, chlorinated compounds, environmental agents, metals (redox and nonredox), ions, and radiation

Valko M, Rhodes CJ, Moncol J, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-Biol Inter. 2006;160:1–40

“A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual. Specifically, drugs such as antibiotics are xenobiotics in humans because the human body does not produce them itself, nor are they part of a normal diet.

Natural compounds can also become xenobiotics if they are taken up by another organism, such as the uptake of natural human hormones by fish found downstream of sewage treatment plant outfalls, or the chemical defenses produced by some organisms as protection against predators.”

http://en.wikipedia.org/wiki/Xenobiotic

Lower reactive oxygen species amount:

Not all reactive oxygen species are harmful. Some reactive oxygen species are beneficial:1. Defense against infectious diseases2. Function of a number of cellular signaling systems

Glade MJ. The role of reactive oxygen species in Health and Disease Northeast Regional Environmental Public Health Center University of Massachusetts. Amerst Nutrition. 2003;19:401–3.

Reactive Oxygen Species Effects

Higher reactive oxygen species amount:

It can mediate damage to cell structures, including lipids and membranes, proteins and nucleic acids; this damage is often referred as “oxidative stress”

Poli G, Leonarduzzi G, Biasi F, et al. Oxidative stress and cell signaling. Curr Med Chem. 2004;11:1163–82

Free radicals can destroy a protein, an enzyme or even a complete cell.

Free radicals can multiply through a chain reaction mechanism resulting in the release of thousands of these cellular oxidants.

The Cells then can become so badly damaged that DNA codes can be altered and immunity can be compromised.

They can cause cell mutations

http://vitanetonline.com/library/Free-Radicals-and-Cancer/

Why Are Free Radicals So Life Threatening?

Possible products of DNA Attack By Reactive Oxygen Species

http://www.fasebj.org/content/17/10/1195.full

http://www.edinformatics.com/interactive_molecules/dna.htm

DNA Attack By Reactive Oxygen Species

(Carcinogenic Compounds )

The reactive oxygen species, the highly reactive hydroxyl radical (•OH) reacts with DNA by addition to double bonds of DNA bases and by abstraction of an H atom from the methyl group of thymine and each of the C-H bonds of 2'-deoxyribose

http://www.ncbi.nlm.nih.gov/pubmed/1798290

Mechanism of DNA Attack By Reactive Oxygen Species

DNA Structurehttp://www.nature.com/scitable/topicpage/discovery-of-dna-structure-and-function-watson-397

http://www.accessexcellence.org/RC/VL/GG/structure.php

http://www.johnkyrk.com/DNAanatomy.html

http://www.alternative-cancer.net/Cell_photos.htm

Pictures of Cancer Cells

http://www.alternative-cancer.net/Cell_photos.htm

Pictures of Cancer Cells

http://www.cancerpictures.net/

Pictures of Cancer Cells

Pictures are too graphic!

http://www.foxnews.com/photoessay/0,4644,4091,00.html/#/photoessay/image/0530081227_M_LaiThiDao450-jpg

Incredible Pictures of Tumors

The body has a defense system called Antioxidants. The antioxidants stop the chain reaction of the free

radicals by the direct reaction with the free radicals and quenching them.

Such Antioxidants are: Vitamin E: (d-alpha tocopherol):

How to Fight Back Free Radicals

http://www.uic.edu/classes/phar/phar332/Clinical_Cases/vitamin%20cases/vitamin%20E/Vitamin%20E%20Chemistry.htm

Your Body

Vitamin C:

http://www.livingintherealworld.net/healthy/2011/07/mr-science-the-chemical-structure-of-vitamin-c/

Beta-carotene:

http://ca.wikipedia.org/wiki/Fitxer:Beta-carotene.png

Regular Exercise (moderation) Taking Vitamin Supplemental (not over supplement) Quit bad habits (smoking, excessive drinking, tobacco

etc…) Good diet (avoiding fats, carbohydrates and similar

food) Vegetables and fruits are natural sources of

antioxidants Avoiding stress and its causes

Your Part in Fighting Free Radicals

https://science.education.nih.gov/supplements/nih1/cancer/guide/understanding1.htm

http://www.parkwaycancercentre.com/about-cancer/how-does-cancer-develop

http://www.ehow.com/how-does_4565263_skin-cancer-occur.html

http://www.medicalnewstoday.com/info/cancer-oncology/

http://www.letusfindout.com/how-does-cancer-attack-the-body/

http://www.edinformatics.com/interactive_molecules/dna.htm

http://www.medicalnewstoday.com/info/cancer-oncology/

http://learn.genetics.utah.edu/content/disorders/whataregd/colon/

Extra References