Download FCC carcenogensis

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 CELL
growth factor
growth factor receptor
cytoplasm
signal transduction
nucleus
activation of
transcription
DNA
RNA
NEOPLASTIC (malignant) CELLS
Increase
in growth
factors
Increase
in growth
factor
receptors
Increase in
signal
transduction
- Distributed processess of mytosis and protein synthesis
Increase in
activation of
transcription
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
Causes
• Environmental agents
• Heredity
Environmental Agents
• 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
Heretidy
• 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
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
chemicals
exposure
to
hazardous
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 precancer to cancer
ROS and various stages of
Carcinogenic Process
Have more cancer protective
substances
• Vegetables, fruits, whole grains, herbs, nuts and
seeds
contain
compounds,
an
abundance
terpenoids,
sulfur
of
phenolic
compounds,
pigments, and other natural antioxidants that
have been associated with protection from
and/or
treatment
of
conditions
cardiovascular disease and cancer.
such
as
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
dependant cancers.
of
hormono-
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)
• Omega-6 Dietary Sources:
Sunflower oil, safflower oil, cottonseed oil, corn oil, &
processed foods made with these oils.
• Omega-3 Sources:
Cold-water fish (i.e., salmon, trout, sardines, herring),
flaxseed, walnuts, pumpkin seeds, canola oil, & soybeans.
• Omega-9 Fatty Acids
Olives, extra-virgin olive oil, canola oil, avocadoes, sesame &
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.