presented by: navdeep kaur apoorva tandon m.sc.(foods and nutrition)3 rd sem

Presented by: Navdeep Kaur Apoorva Tandon M.Sc.(Foods and Nutrition)3 rd sem.

1. Introduction 2. Biology of cancer 3. Causes of cancer 4. Factors increasing cancer risk 5. Metabolic effects of cancer 6. Types/Sites of cancer 7. Free radicals 8. Formation of free radicals 9. Free radicals in biological system 10. Antioxidants 11. Classification of antioxidants 12. Absorption of antioxidants 13. Enzymes as antioxidants in cells 14. Plasma antioxidants 15. Cellular antioxidants 16. Antioxidant vitamins (A,C,E) 17. Neutraceuticals 18. Isothiocyanates (Cruciferous vegetables) 19. Allium foods( diallylsulfide) 20. Chemotherapy 2

INTRODUCTION CANCER----->>> CRAB 2 nd leading cause of death. Age- a major determinant of risk Characterized by abnormal cell growth Reproduction is unstructured and excessive Leads to Tumor/ Neoplasm More than 100 types known 90% being due to avoidable factors 3

Biology of Cancer By Development of cells, : escaped normal regulation of growth, :normal replication and differentiation :which invades surroundings. Cellular and tissue integrity,>>>> series of processes :cell division and DNA replication :growth and differentiation :apoptosis(cell death) 4

Cancer develops when---- cells acquire the ability to escape that regulation. Cancer cells display characteristics/ capabilities (not present in normal cells) which affects :cell growth :replication :interaction with neighboring cells :interaction with environment 5

Genetic change in single cell, its uncontrolled multiplication. The 2 Types of regulatory genes involved in the development of cancer: oncogenes antioncogenes Oncogenes are the cancer causing genes. Cancer suppressor genes or antioncogenes regulate cell proliferation. *their loss removes growth control of cells-->>several tumors 7

Types of Tumors Benign Do not spread Can be often removed Malignant Spread to other parts of the body Difficult to remove 8

The growth of malignant tumor is a long, slow process that involves 3 key steps : 1. Initiation of potentially cancerous changes in a cells DNA. 1. The promotion uncontrolled growth in a damaged cell. 1. The progression of a cancerous lesion into a mass that can invade other tissues. 9

ETIOLOGY / CAUSES 10

A cause of any disease is any usual exposure that, if removed, reduces the likelihood of the disease developing, or its severity. -A factor that alone can result in disease is called sufficient cause; if more than one factor is required,these are termed as contributory causes; if a disease cannot occur in the absence of a factor, then necessary cause. 11

CAUSES CHEMICAL CARCINOGENS RADIATION ENERGY VIRUSES 12

Almost 80% of human cancers are caused by chemical carcinogens in nature. Entry 0f chemical in body may be due to. Occupation (asbestos,benzene) Diet (contaminated food) Drugs (diethylstilbestrol) Life style(smoking) 13

Chemicals Occupation Life style DrugsDiet 14

Some of chemicals on their own are not carcinogenic. Certain substances known as promoting agents make them carcinogenic. Example:Application of benzo-(a)pyrene to the skin, as such not cause tumor development, however if this is followed by the application of croton oil, tumors develop.here,croton oil acts as a promoting agent or promoter. 15

RADIATION 16

Radiation damage to genes may come from x-rays, radio active materials, atomic exhausts or wastes, or from sunlight. UV rays, X-rays and gamma-rays have been proved to be causing cancers. These rays damage DNA which is the basic mechanism to explain the carcinogenicity of radiation energy. X-rays cause the production of free radicles,which is responsible for the carcinogenic effects of radiation. 17

Carcinogenic viruses ROUS /1911 18

Tumor inducing virus, interfering with the function of regulatory genes have been identified. 19

Disease viruses act as parasites, taking over the the cell machinery to reproduce themselves. 20

Stress factors 21 Stressful states make a person more vulnerable to other cancer producing factors through their influence on the- Integrity of the immune system Food behavior Nutritional status

FACTORS Environmental Carcinogenic chemicals Occupational Food contamination Smoking Pollution Infectious agents Viruses Bacteria Fungi 22

23 Types of cancer

24 MOUTH/ PHARYNX CANCER MOUTH CANCER

MOUTH/ PHARYNX CANCER Accounts for about 6% worldwide, common in developing countries. Salted fish consumption enhances the risk of nasopharynx cancer & betel nut chewing that of oral cancer. Excessive consumption of alcohol & smoking enhance risk of cancer in all sites. Fruit has a protective role in these cancers, according to study. Effect of vegetable is less consistent 25

MECHANISM-: 26 ALCOHOL ALDEHYDE & N- NITROSO COMPOUNDS CARCINOGENS ALCOHOL CELL PROLIFERATION LIPID PEROXIDATION ACTIVE PROCARCINOGENS

OESOPHAGUS CANCER Its very according to nutritional status of people. Obesity, Alcohol & smoking are most important factor. Obesity might leads the increasing rates of tumor, and may be affect the gastro esophageal. Poorly stored corn by toxin from fungus also cause this. fruits and vegetables are good in lowering the risk. 27

STOMACH CANCER Its about 2-4% every year. Rates in men are double than women. High salt consumption is a causative factor. Fruit &vegetables lower 50% risk. Highest rates in Japan. Lowest rates in Gambia & Kuwait. 28

Beta carotene Vitamin E Selenium Low Stomach cancer 29

LARGE BOWEL CANCER Second most cancer in many societies. Affect up to 6% of men & women by age of 75. Highest risk in Australia, new Zealand,USA,parts of N.Europe. Lower risk in Africa, China& INDIA. It is strongly +vely associated with fat meat consumption. Strongly vely associated with starch& vegetables consumption. In men overweight is also at risk. Exercise reduce the risk at some level. 30

The role of colonical microbial flora is central To the causation of cancer. the flora is large & diverse & dependent on residues for nutrition. 31

33 STARCH SUGAR CHO Anaerobic fermentation

SCFA Acetate propionate Butyrate Increase in microbial cell mass 34

MECHANISM: 1. CHO having no. of implications for protection agents large bowel cancer. Increase stool weight. Dilution of colonical contents in gut. Faster transit time. 35 Low stool weight Constipation cancer

2.One of the SCFA butyrate is of particular interest because It is anti proliferative agent. Arresting cell growth. Inducing differentiation in cell lines. 3.Studies shown that BRAN appeared to have consistency protective affect against chem- carcinogensis. Soluble fiber are associated with tumor enhancement. 36

37 Fat Bile acid flora Deoxycholic acid cancer

LUNG CANCER The most common cancer in the world. Cause cigarette smoking. HYPOTHESIS: lung cancer risk can be suppressed by beta-carotene & vitamine,found in fruit & vegetables by studies. 38

BREAST CANCER Commonest cancer in women. Risks increases with age, but there is a decreases rate of increases in incidence after the menopause. Early menopause Late menopause Late 1 st pregnancy 39

METABOLIC EFFECTS Cancer cachexia In advance disease,this complex metabolic syndrome is a major cause of morbidity & mortality. Anorexia Early satiety Weight loss Wasting Weakness,characterize the syndrome. Alteration in energy,CHO,proteins and fat metabolism, acid base balance,enzyme activities,enodocrine homeostasis& immunologic states are seen. Metabolic rate usually increases in leukemia. 40

Impaired glucose tolerance Decreased insulin production Insulin resistance. Skeletal muscle mass is reduced. Hypoalbuminemia. Negative nitrogen balance in spite of sufficient intake. Urinary excretion of Na & K is increased. 41

ANOREXIA Frequent finding in advanced cancer. Weight loss is due to reduction in food intake associated with anorexia. Alteration in taste & smell are advance in cancer. Some having increase threshold for sweet or sour taste. Some additives make food more acceptable to these patients Subsection of protein sources so that protein intake is not compromised. 42

Nutritional Needs Energy Hypermetabolic nature and its healing requirements place greater energy demands on the cancer. Adult patient---- 2000 kcal or 25-30 kcal/kg If malnourished---- 2500-3000 kcal or 35-40 kcal/kg, or more, depending on the extent of tissue injury. Protein Necessary tissue building for healing and to offset tissue breakdown by the disease requires essential amino acids and nitrogen. Adult patient----80-100 gm ( high quality) If malnourished----100-150 gm, to restore negative nitrogen balance. 44

Vitamins and minerals - They also play important role in building and maintaining strong tissue. Thus an optimal intake of vitamins and minerals is needed. Fluid Adequate fluid must be ensured for : i. to replace gastrointesinal losses from fever, infection, vomitting or diarrhoea. ii. To help kidneys dispose off metabolic breakdown products from destroyed cancer cells and from toxic drugs used in chemotherapy. 45

Fiber Dietary fiber is postulated to exert a protective effect against colon cancer by several mechanisms. It has a possible role in prevention of colon cancer by decreasing transit time, so that in contact with the colon for a shorter time which reduces the contact of carcinogens in the colon wall. Selenium- high levels of selenium intake have been found to be anti tumorigenic. It has been found to be beneficial in the fight against free radicals. Sea foods, grains, muscle meats have the highest concentrations of selenium. 46

Medical treatments Three major forms of therapies are used today as medical treatment for cancer: 1. Surgery an operation to remove or repair part of the body to diagnose or treat cancer. May be used as the only mode or in combination chemotherapy or radiation therapy. 47

Impact of surgery SITESYMPTOMS Oral cavity Difficulty in chewing and swallowing Sore mouth Alterations in taste and smell Larynx Alterations in normal swallowing Lung Shortness of breath Stomach Dehydration Early satiety Pancreas Hyperglycemia Vitamin and mineral malabsorption 48

Nutritional therapy for this treatment Nutritional supplements drinks Enteral nutrition (feeding through a tube into the stomach or intestine) Medications to improve the appetite 49

2. Radiation therapy It is a cancer treatment that uses high energy X- rays or other types of radiation to kill cancer cells. Most severely it damages the cells that are actively dividing and making new DNA such as tumor cells. 50

Impact of Radiation Therapy SITESYMPTOMS Brain and spinal cord Nausea Vomiting Fatigue Headache, lethargy Larynx Sore mouth and tongue Alterations in taste and smell Ulceration Thorax Dysphagia Heartburn Loss of appetite Dry cough Abdomen and pelvis Lactose intolerance Loss of appetite Diarrhoea Maldigestion 51

Nutritional therapy Nutritional supplements Eating small meals Enteral nutrition 52

3. Chemotherapy It is the use of chemical agents or medications to treat cancer. Cytotoxic drugs destroy cancer cells by interfering with the synthesis and function of nucleic acids in the cells. Healthy cells can also be damaged. Bone marrow, hair follicles, and mucosa of the alimentary tract are most susceptible to damage. 53

Impact of chemotherapy CYTOTOXIC DRUGSSYMPTOMS Anorexa Vomiting Fatigue Nausea Vomiting Diarrhoea Fatigue Glucose intolerance Osteoporosis Nausea Fluid retention Hot flashes Nausea 54

Free Radicals and Antioxidants 55

OXYGEN Existence Toxic and damages tissues [ Not synonyms ]Not synonyms Free radical 1 or more unpaired electrons in its outer orbit( R ) Electron imbalance High reactivity For more stable species, eg. NO, NO2 56 High concentrations

57 Generation of ROS Antioxidant defences Superoxide [O2] Hydroxyl radical [OH] Singlet oxygen [O2] Hypochlorous acid [HOCl]

Antioxidants in Food Neutralize free radicals in food Protection from diseases 58

Formation of Free Radicals By-products of aerobic cellular metabolism O2 + e - O 2 - (Superoxide radical) Free radicals Environmental pollutants OzoneSunlight 59

a) o 2 + e - 0 2 - (superoxide radical) b) Fe 2+ + 02 Fe 3+ + o 2 - (superoxide radical) c) o 2 - +e - + 2H + H2O2 d) o 2 - + o 2 - + 2H + H2O2 + O2 e) H2O2 + e- +2H+ H2O + OH (hydroxyl radical) f) Fe 2+ +H2O2 Fe 3+ + OH - + OH g) o 2 - + H2O2 O2 + OH - + OH Fe salt catalyst 60 BACK

Common characteristic features of free radical are: Highly reactive Very short half life Can generate new radicals by chain reaction Cause damage to biomolecules, cells and tissues 61

Free Radicals in Biological System ABA B BCB C Non-radical 62 Slide 28

Damage Protein Breakage of DNA strands Initiate lipid peroxidation OH - 63

Damage to thousands of fatty acid molecules & Formation of Fatty acid peroxyl radicals Lipids, proteins, nucleic acids 64

Anti-oxidants in Biological System 65

Classification of Anti-oxidants Lipid peroxidation-- 66

Nature and action-- 67

Location-- Intracellular anti-oxidants Catalase, glutathione peroxidase, superoxide dismutase 68

Absorption of Antioxidants Vitamin A: Vitamin C: Rapidly absorbed from the intestine. It is not stored in the body to a significant extent and is excreted in the urine as such. 69

Vitamin E: Absorbed along with fat in the small intestine 70

Important Cancer Antioxidants 72 Vitamin status Risk for cancer

Anti-oxidant Vitamins(A,C,E) and cancer 73 Low intakes of vitamin A from fruits and vegetables or low levels of retinoids resulted in increased risk for certain cancers. (esp. lung cancer) The mechanism through which vitamins inhibit tumorigenesis has not been explained, but 3 levels at which these act are known.

as inhibitors of carcinogenic precursors. as blocking agents preventing carcinogens from acting at a target site. as supressing agents that diminish the effect of a carcinogen already present. 74

Inverse associations between: Lung,Oral, esophageal, bladder, reproductive, stomach cancer. Vitamin A Colon, esophageal, stomach, lung,oral cancer. Vitamin C Lung, breast cancer. Vitamin E 75

76 Antioxidants are abundant in fruits and vegetables, as well as in other foods including nuts, grains, and some meats, poultry, and fish.

Enzymes as Antioxidants Superoxide dismutase (SOD) is one of the important enzymes that function as cellular antioxidants. Present in cell cytoplasm and in mitochondria. Catalyses dismutation of superoxide anion, 2 O2 - + 2H + O2 + H2O2 77 Lethal Absence Detrimental Too much Production of H2O2 at toxic rate

Extracellular form of SOD exists in plasma, lymph and synovial fluid. Functions at cell surfaces Catalase, is a heme protein that catalyses the reaction in which H2O2 is detoxified 2H2O2 O2+ 2H2O 78

Plasma Antioxidants Most important antioxidant proteins of plasma include--- Bilirubin (bound to albumin) and uric acid are good scavengers of oxyradicals. 79 CeruloplasminAlbuminTransferrin HemopexinHaptoglobin

Neutraceuticals Foundation of Innovation in Medicine defined them as--- Any substance considered a food or part of a food that provides medical or health benefits, including prevention or treatment of diseases. Food components trigger the enzymes that block or supress DNA damage and reduce tumor size. 80

Hghj Free radicals Precarcinogens 81 DNA Vitamin E,C; carotenes; tea; tomatoes. Carcinogens Phase 1 Garlic etc. inhibit this reaction DNA damage Inactive compounds Cauliflower, broccoli etc. stimulate this reaction

Allium foods 82 Allium vegetables are members of the lily family and include: Garlic Onion Leeks

presented by: navdeep kaur apoorva tandon m.sc.(foods and nutrition)3 rd sem

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