Carcinogenesis

• It is a genetic disease

• Either acquired genetic abnormality or inherited

genetic abnormality

• It arises when several mutations accumulate

within genome

Carcinogenesis---- Neoplasia

• The process of transformation from a normal cell to a cancerous one

• Neoplasia is an abnormality of cell growth and multiplication characterised by:

• At cellular level – Excessive cellular proliferation/propagation– Uncoordinated growth– Tissue infiltration/penetration

• At molecular level – Disorder of growth regulatory genes

What is a carcinogen?• A substance or agent known to cause

cancer or produces an increase in incidence of cancer in animals or humans

• Carcinogens may be chemical substances; physical agents, or biological agents

• carcinogenic substances may be inhaled, absorbed through the skin or ingested.

A carcinogen can alter or damage a cell’s DNA…

• A carcinogen may be the initiator —

the agent that alters or damages

DNA, the basic coding system of cells

• It may also be promoter —

encouraging out-of-control cell

growth

Cancer

• Cancer refers to a number of diseases characterized by uncontrolled growth and spread of abnormal cells.

NORMAL CELLgrowth factorgrowth factor receptor

signal transduction

activation of transcriptionDNA

RNA

cytoplasm

nucleus

NEOPLASTIC (malignant) CELLS

Increasein growth factors

Increasein growth factorreceptors

Increase in signal transduction

Increase in activation of transcription

- Distributed processess of mytosis and protein synthesis

Malignant Cells

• Continuous reproduction

• Formation of abnormal proteins

Origin of neoplasis

• two general types of hypothesis– Monoclonal

• initial neoplastic change affects a single cell

– Field origin• carcinogen acts on large number of cells

producing field of potentially neoplastic cells

Regulatory genes

NEOPLASIA proto-oncogene is activated or tumor suppressor gene is inactivated

Activation of proto-oncogene: – point mutation– translocation– gene amplification

- Failure of Immune Surveillance theory : immune system responds to neoantigens as to foreign antigens, but neoplastic cells escape recognition and destruction --> become clinical cancers

Regulatory genes

Proto-oncogenes (activated oncogenes)

- colon cancer - lymphoma - chronic myelogenous leukemia Tumor suppressor genes - retinoblastoma

• Environmental agents

• Heredity

Causes

• Chemical carcinogens:– hydrocarbons (cigarette smoke, automobile exhaust

gases)– insecticides– dyes– industrial chemicals– insulation– Hormones E.g. - DES (diethylstilbestrol)/estrogen

drugs

Environmental Agents

• Radiation:– sunlight– X-rays– radioactive substances– nuclear fusion

• Energy interacts with DNA causing its damage and mutation, which leads to CANCER

• E.g.

- leukemia (radiologists, atomic bomb survivors)

- skin cancer – UV radiation from the sun

Environmental Agents

• Viruses (oncogenic viruses)

– HTLV – causes a form of leukemia in adults

– Herpes VIII – Kaposi sarcoma

– Papilloma virus – cervical carcinoma

– Epstein-Barr virus – lymphoma

Environmental Agents

• Transmission of some forms of cancer from parents to offspring through defects in the DNA of the egg or sperm cells

• E.g. Retinoblastoma – tumor of the retina of the eye

Polyposis coli syndrome – polyps that grow in the colon and rectum

Other colon, breast and kidney cancers

Cause: loss of a segment of DNA or a change in the coding sequence of DNA

In many cases – abnormalities in tumor suppressor genes

Heretidy

Genetic Screening

• detection of inherited cancer-causing gene by

testing the blood cells of family members

(inherited changes can be detected in all tissues

of the body, not only cancerous cells)

Cancer is a global concern

• Cancer incidence is on the rise

worldwide

• World Health Organization estimates

that 80 per cent of cancers are

caused by occupational or

environmental factors, including

exposure to hazardous chemicals

Chemicals the worst culprits

• Chemical substances constitute the largest group of carcinogens

• New chemical substances are being developed every year, often without prior testing on their potential toxic effects

International research tracking

down carcinogenic substances

• International agencies such as the UN’s International Agency for Research on Cancer (IARC), are continually updating lists of known and suspected carcinogens.

• International Agency for Research on Cancer www.iarc.fr

Natural carcinogens

• National Research Council has reported that

excess calories pose more of a cancer

threat than natural or synthetic

carcinogens in food

Naturally-occurring Carcinogens• Aflatoxins and Ochratoxin A are natural toxins

made by fungal food contaminants cause cancer in animals and humans.

• Safrole, which is found in sassafras tea, cinnamon, cocoa (trace), and other herbs and spices is a liver carcinogen in rats.

• Heterocyclic amines in cooked meats have been associated with stomach and other cancer formation.

• Asbestos (naturally occurring silicate mineral) increases the risk of lung cancer.

• Tobacco smoke (lung cancer)• alcohols (liver cancer).

Cancer Prevention by Phyto-chemicals

• Phyto-chemicals appear to have the ability to

stop the conversion of a cell from healthy to

cancerous at different stages.

• Antioxidants stop free radicals (reactive oxygen

species, ROS) from harming a healthy cell

• Plant defenders can slow the process from pre-

cancer to cancer

ROS and various stages of Carcinogenic Process

Have more cancer protective substances

• Vegetables, fruits, whole grains, herbs, nuts and

seeds contain an abundance of phenolic

compounds, terpenoids, sulfur compounds,

pigments, and other natural antioxidants that

have been associated with protection from

and/or treatment of conditions such as

cardiovascular disease and cancer.

Cancer protective and anticancer plants

Garlic: • Organosulfur compounds originating from garlic

inhibit carcinogen activation, boost detoxifying processes

CURCUMA (Turmeric)

• Curcumin, a natural component one of the most powerful chemo-preventive and anticancer agents.

• Its biological effects range from antioxidant and anti-inflammatory

Ginger

• Some pungent constituents (gingerol, zingerone and paradol ) present in ginger exhibit cancer preventive activity.

Liquorice • a flavonoid found in licorice, has been

identified as a potent anti-tumor promoting agent

Ginseng root

• Ginsenoside a metabolite of ginseng, may be

applied as a potential therapeutic agent in the

prevention and treatment of cancer.

Fenugreek

• A naturally occurring edible spice as an

anticancer agent.

• The extract from the seeds of fenugreek, is

cytotoxic in cancerous cells.

Green tea

• catechin in green tea, appears to be the most

biologically active constituent in tea with respect to

inhibiting cell proliferation in cancer cells.

Flaxseed oil

• Flax lignans belonging to the phytoestrogens are

metabolised after ingestion into enterolignans

that may offer a protection against the onset and

development of hormono-

dependant cancers.

Sesame Seed • The mammalian lignans, which are produced by

the microflora in the colon of humans and

animals from precursors in foods, have been

suggested to have potential anticancer effects

• Sesame seed, alone and in combination with

flaxseed, produces mammalian lignans

equivalent to those obtained from flaxseed alone.

Soybean• Populations consuming high levels of soybean

products have both lower cancer incidence and mortality rates in the western countries.

• The soy isoflavones have antiproliferative effects on a variety of cancer types.

• Lunasin of soy is a novel seed peptide for cancer prevention

Soybean• Genistein is an isoflavone can act against human

breast cancer tumours in vivo

Cruciferous vegetables

• Indole-3-carbinol (I3C), a naturally occurring

compound found in vegetables such as broccoli

and cabbage, is a promising anticancer agent

human lymph node carcinoma of prostate.

• Cruciferous vegetables decreased the risk of

breast cancer by 40 percent.

Tomato

• high consumption of tomatoes effectively lowers the risk of reactive oxygen species (ROS)-mediated diseases such as cardiovascular disease and cancer by improving the antioxidant capacity.

• Tomatoes are rich sources of lycopene, an antioxidant carotenoid reported to be a more stable and potent singlet oxygen quenching agent compared to other carotenoids

Wheat germ and whole grains

• Tocotrienols are naturally occurring compounds highly enriched in palm oil, rice bran, oat, wheat germ, barley and rye.

• have antioxidant properties as well as potent anticancer properties.

• Fibers in the bran is colon-protective

Citrus fruits• flavonoids have a protective effect against

cardiovascular diseases and some types of cancer.

• Limonoids are a prominent group of secondary metabolites in citrus fruit with anticancer effect

Spinach leaves

• Spinach leaves, containing several active components, including flavonoids, exhibit antioxidative, antiproliferative, and antiinflammatory properties in biological systems.

• The glycolipids fraction from spinach is potentially a source of food material for a novel anticancer activity

Strawberry

• The most abundant phytochemicals are ellagic acid, and certain flavonoids: anthocyanin, catechin

• Compounds in strawberries have demonstrated anticancer activity in several different experimental systems, blocking initiation of carcinogenesis, and suppressing progression and proliferation of tumors.

Change your lifestyle to be more protected

• It has been estimated that 30-40 percent of all cancers can be prevented by lifestyle and dietary measures alone.

• Try to avoid carcinogens and factors increasing cancer risk.

• Have more cancer protective substances and be physically active.

Factors increasing cancer risk

• Obesity.

• Nutrient sparse foods such as concentrated sugars and refined flour products that contribute to impaired glucose metabolism (which leads to diabetes).

• Low fiber intake.

• Consumption of excess red meat, saturated fats & the imbalance of omega 3 and omega 6 fats.

• Regular consumption of alcohol and tobacco

Essential Fatty Acids (EFA)Essential Fatty Acids (EFA)• Omega-6 Dietary Sources:Omega-6 Dietary Sources:

Sunflower oil, safflower oil, cottonseed oil, corn oil, & Sunflower oil, safflower oil, cottonseed oil, corn oil, & processed foods made with these oils.processed foods made with these oils.

• Omega-3 Sources:Omega-3 Sources:Cold-water fish (i.e., salmon, trout, sardines, herring), Cold-water fish (i.e., salmon, trout, sardines, herring),

flaxseed, walnuts, pumpkin seeds, canola oil, & soybeans.flaxseed, walnuts, pumpkin seeds, canola oil, & soybeans.

• Omega-9 Fatty AcidsOmega-9 Fatty Acids Olives, extra-virgin olive oil, canola oil, avocadoes, sesame & Olives, extra-virgin olive oil, canola oil, avocadoes, sesame &

almonds.almonds.

Some valuable advice

• Enjoy fruit as a snack or dessert

• Add fruits to breakfast cereal

• Try whole-grain or multigrain toast and sandwiches

• Eat three different colors of vegetables with dinner

• Fill half of the dinner plate with vegetables

• Include salad with lunch

Some valuable advice

• Add sweet corn to salads

• Limit red meat to 3-4 serves each week

(a serve of meat is 65-100 grams)

• Choose fish, skinless chicken, legumes, eggs or nuts on the other days

• Try a new vegetarian meal every week

• Limit processed meats

• Select foods low in fat

• Try a wide variety of vegetables and fruits.