2. CANCER
• CANCER DISEASE- IN WHICH CELL GROW ABNORMALLY –MALIGNANT NEOPLASM
• (NEW GROWTH )-NEOPLASIA
• A MASS OF TISSUE ---ABNORMAL ,EXCESSIVE,UNCORDINATED ,PURPOSELESS
PROLIFERATION
• ONCOLOGY = ONCOS ( TUMOR ) + LOGY (STUDY )
• BENIGN TUMOR---THAT DOSE NOT INVADE /SPREAD –NON CANCEREROUS
• MALIGNANT TUMOR /CANCER –INVADES DESTROY TISSUE IN WHICH ORIGINATES
–CAN SPREAD IN OTHER TISSUES VIA BLOOD STREAM & LYMPHATIC SYSTEM
3. PROPERTIES OF CANCERCELLS
• UNRESTRAINED GROWTH
• INVANSION OF LOCAL TISSUE
• METASTASIS
MORPHOLOGICAL CHANGES
SHAPE ---ROUNDER
MOTILITY ---LOSS OF CONTACT INHIBITION OF MOVEMENTS
GROWTH --- LOSS OF CONTACT INHIBITION –MULTILAYER /NUMBER OF NUCLEI
BIOCHEMICAL CHANGES
ALTERED GENE REGULATION ---DNA SYNTHESIS ---RNA SYNTHESIS ---PROTEIN
SYNTHESIS---ANABOLISM---GROWTH
4. BIOCHEMICAL CHANGES
ALTERED GENE REGULATION
INCREASED DNA SYNTHESIS
INCREASED RNA SYNTHESIS
INCREASED PROTEIN SYNTHESIS
ANABOLISM---GROWTH FACTORS &HORMONES
INCREASED AEROBIC & ANAEROBIC GLYCOLYSIS
SYNTHESIS OF LACTIC ACID & LACTIC ACIDOSIS
ALTERATION OF CELL SURFACE DUE CHANGES IN COMPOSITION OF
GLYCOPROTEINS & GLYCOSPHINGOLIPIDS
DECREASED
8. PHYSICAL CARCINOGENS
• RADIENT ENERGY ---UV LIGHT ,IONIZING RADIATIONS
• EXAMPLS –SUNLIGHT ,WELDERS ARC ,UV LAMPS ---SKIN CANCER
• FORMATION OF PYRIMIDINE DIMER IN DNA STRAND
• FORMATION OF APURINIC OR APYRIMIDINE SITE ELIMINATION OF BASES
• BREAKING OF CROSS LINKING OF SINGLE OR DOUBLE STRAND OF DNA
IONIZING RADIATIONS –X RAYS ,ALPHA ,BETA ,GAMMA RAYS ,RADIOACTIVE
ISOTOPES ,PROTONS ,NEUTRONS
• IONIZING RADIATIONS---DAMAGE DNA ,DISLODGE IONS FROM H2O&
BIOMOLECULES ,INTERACT WITH PROTEINS, DNA-----CANCER
(MUTAGENESIS)
13. WHAT IS A CARCINOGEN?
Any substance that is capable of causing cancer.
Cancer is the abnormal or uncontrolled growth of new cells in any part of
the body, characterized by cells that tend to invade
surrounding tissue and metastasize to new body sites.
Carcinogens are chronic toxins. They cause damage after repeated or long-
duration exposure. They may have not immediate apparent
harmful effects, with cancer developing only after a long latency period.
15. WHAT ARE REPRODUCTIVE TOXINS?
Mutagens
cause damage to chromo- somes
by introducing changes to DNA.
Mutagens have adverse effects
on fertility and general
reproductive performance.
Mutagens are chronic toxins
Teratogens
act during pregnancy to cause
adverse effects on the embryo or
fetus including malformations,
retarded growth and post- natal
deficiencies.
Reproductive toxins can affect
both men and women.
16. WHAT MATERIALS ARE CARCINOGENS?
Asbestos
Certain chemicals
Coal tars and coke oven emissions Hardwood
sawdust (certain species) Ionizing radiation
Natural products (progesterone, safrole) Tobacco
smoke
Ultraviolet radiation
17. WHAT IS A CHEMICAL CARCINOGEN?
Any discrete chemical compound which has been shown
to cause cancer in human or animal studies.
Hundreds of individual compounds have been shown
to induce cancers. Many thousands of
additional compounds are “suspect” carcinogens.
Many are commonly used in laboratory operations,
shops and art studios.
18. HOW IS CHEMICAL CARCINOGENICITY DETERMINED?
Epidemiological studies determine the relationship between a cancer
suspect chemical and a human population over a long period of time.
Animal studies directly induce cancer in test animals using a large sample of
animals, usually of two or more species with varying dose and time
parameters.
Experiments with animals are based on the premise that chemicals that
produce cancer in animals will have similar effects on human cells.
Most known human carcinogens produce cancer in
experimental animals.
20. CLASSES OF CARCINOGENS (CONT.)
Misc. organic compounds:
Formaldehyde Acetaldehyde
1,4-Dioxane Ethyl
carbamate 2-Nitropropane
Styrene Thiourea
Thioacetamide
Misc. inorganic comp.: Arsenic
and compounds Chromium and
comp.
Thorium dioxide Beryllium and
compounds Cadmium and
compounds Lead and compounds
Nickel and compounds Selenium
sulfide
21. HOW DO CARCINOGENS ENTER THE
BODY?
Skin absorption. Many solvents and other chemicals
go directly through the skin.
Ingestion. Swallowing of a carcinogen.
Inhalation. Breathing gases, fumes and vapors is the
most common form of exposure.
22. WHAT ORGANS TO CARCINOGENS ATTACK?
Lungs Liver
Kidney
Reproductive system Skin
Many other organs and tissues
23. WHAT FACTORS INFLUENCE THE DEVELOPMENT OF CANCER?
Dose--amount and length of exposure. The lower the dose the
least likely you are to develop cancer or related diseases.
Environmental or “lifestyle” factors.
Cigarette smoking (co-carcinogen) Alcohol consumption
(co-carcinogen)
Diet--high fat consumption, natural antioxidants Geographic
location--industrial areas, UV light Therapeutic drugs--some are
known carcinogens Inherited conditions
24. HOW DO I REDUCE MY EXPOSURE TO CARCINOGENS?
Engineering controls--exhaust ventilation and equipment Personal
protective equipment
Personal hygiene
Labeling and storage of containers Housekeeping
and maintenance Regulated areas
Decontamination and emergency procedures Monitoring
Administrative controls
25. ENGINEERING CONTROLS--EXHAUST VENTILATION AND EQUIPMENT
Fume hoods--full open face velocity of 80 to 100 f.p.m.
Local ventilation--exhaust (sometimes supply) at the point of use of a
chemical. “Elephant trunk” or slot hood.
Carcinogen glove box or environmental chamber. Biosafety cabinet--
used for anticancer drugs, viruses. No benchtop work in a laboratory
setting.
26. PERSONAL HYGIENE
No smoking, eating, drinking or application of cosmetics is permitted in areas
where carcinogens are in use (or in any lab area!). No mouth pipetting!
Wash hands and any exposed skin if potentially contaminated--
face, neck, forearms, etc.
No shorts or open toed shoes.
Remove lab coat or other potentially contaminated protective clothing
before leaving the work area.Lab coats need to be cleaned regularly;
special washing instructions may be needed. Contaminated
disposable clothing should be treated as hazardous waste
27. HOW DO I DISPOSE OF WASTE CARCINOGENS?
Carcinogens may never be disposed of in the ordinary
trash or be discharged to the sanitary sewer.
Waste bottles must be properly labeled, tightly capped
at all times (except when adding or removing waste)
and they must have secondary containment.
29. APOPTOSIS
• Dropping /falling of the normal programmed destruction of cells
.,during embryogenesis, development of adult life.
• Destruction of apoptosis promote inappropriate cell division ,cell
survival ---development of cancer
31. ONCOGENE
EXPRESSION
proto –oncogenes control normal growth &cell division
Mutated versions of proto-oncogenes act as oncogenes
examples
• Growth factors
• Growth factor receptors
• Protein involved in signal transduction(protein kinase that phosphorylates
tyrosine /serine residue )---GTP binding protein
• Proteins involved in signaling gene expression in nucleus
• some growth factor induce growth but not cell division –cell grows large in size
without ever dividing
• 50 types of growth factors identified –first platelet diving growth factor(PDGF)
32. MECHANISMS OF ACTIVATION OF PROTO-ONCOGENES
TOONCOGENES
• Promoter and enhancer insertion
• Chromosomal translocation
• Gene amplification
• Point mutation
• Effect of oncogene on growth ---putting one foot on accelerator of
automobile
• Tumor suppressor gene ---taking one foot from the break
33.
34. TUMOR
MARKERS
• DEFINITION –BIOLOGICAL SUBSTANCES SYNTHESIZED OR RELEASED
BY CANCER CELLS AND FOUND IN INCREASED AMOUNT IN BLOOD
,BODY FLUID OR TISSUES INDICATING PRESENCE OF CANCER
35. APPLICATIONS OF TUMOR MARKERS
• DIAGNOSIS (SCREENING )
• DIFFENTIAL DIAGNOSIS
• STAGING OF CANCER
• DETECTION OF RECURRENCE
• MONITORING RESPOSE TO THERAPY (PROGNOSIS)
36. TUMOR
MARKERS
ENZYMES
PROSTATIC ACID PHOSPHATASE---PROSTRATE CANCER
ALKALINE PHOSPHATASE --- BONE SECONDARIES
PROTEINS
• PROSTRATE SPECIFIC ANTIGEN----PSA--PROSTRATE CANCER
• MULTIPLE MYELOMA----SERUM PROTEIN IMMUNOGLOBULIN/BENCE JONES PROTEINS
• C PEPTIDE ---INSULINOMA
• BETA MICROGLOBULINS –BETA CELL LYMPHOMAS
CARBOHYDRATE
• CARBOHYDRATE ANTIGEN (CA—125)—OVARIAN ,ENDOMETRIUM
• CARBOHYDRATE ANTIGEN (CA—549)—BREAST ,OVARIAN