CARCINOGENESIS

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CARCINOGENESIS

• Niko Blaževic
• Mentor A. Žmegac Horvat

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Definition
Carcinogenesis

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

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Neoplasia
Carcinogenesis

• Neoplasia is an abnormality of cell growth and
  multiplication characterised by
• At cellular level
• Excessive cellular proliferation
• Uncoordinated growth
• Tissue infiltration
• At molecular level
• Disorder of growth regulatory genes

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Carcinogenesis
NORMAL CELL
growth factor growth factor receptor
cytoplasm
signal transduction
activation of transcription
DNA
nucleus
RNA
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Carcinogenesis
NEOPLASTIC (malignant) CELLS
Increase in growth factor receptors
Increase in activation of transcription
Increase in growth factors
Increase in signal transduction
- Disturbed processes of mitosis and protein
synthesis
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Malignant cells
Carcinogenesis

• Continuous reproduction
• Formation of abnormal proteins
• ANAPLASIA
• loss of normal cell function (abnormal DNA
  transcription)
• proliferation
• movement of cells
• invasion of nearby tissue
• metastasis

Caused by altered DNA and altered cellular
programs which make new signals
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Hypotesis of the origin of neoplasia
Carcinogenesis

• two general types
• Monoclonal
• initial neoplastic change affects a single cell
• Field origin
• carcinogen acts on large number of cells
  producing field of potentially neoplastic cells

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Regulatory genes
Carcinogenesis

• Proto-oncogenes (activated ? oncogenes) code
  for
• growth factors
• receptors
• signal-relay or transduction factors
• ras - colon cancer
• myc - lymphoma
• bcr-abl - chronic myelogenous leukemia
  (Philladelphia chromosome)
• Tumor suppressor genes - code for factors
  that down- regulate the cell cycle, promote
  differentiation and supress oncogenes from
  causing cancer
• Rb-1 retinoblastoma gene
• p53

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Carcinogenesis

• NEOPLASIA ? proto-oncogene is activated or tumor
  suppressor gene is inactivated
• normal growth ?
  oncogenesis
• Activation of proto-oncogene
• point mutation
• translocation
• gene amplification
• Also - Failure of Immune Surveillance theory
  immune system responds to neoantigens as to
  foreign antigens, but neoplastic cells escape
  recognition and destruction --gt become clinical
  cancers

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Causes
Carcinogenesis

• Environmental agents
• Heredity

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Environmental agents
Carcinogenesis

• Chemical carcinogens
• hydrocarbons (cigarette smoke, pipe smoke,
  automobile exhaust gases)
• insecticides
• dyes
• industrial chemicals
• insulation
• hormones
• E.g. - DES (diethylstilbestrol)
• - estrogen drugs

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Environmental agents
Carcinogenesis

• 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

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Environmental agents
Carcinogenesis

• Viruses (oncogenic viruses)
• HTLV causes a form of leukemia in adults
• Herpes VIII Kaposi sarcoma
• Papilloma virus cervical carcinoma
• Epstein-Barr virus Burkitt lymphoma
• Two types RNA and DNA viruses

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Heredity
Carcinogenesis

• 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
• Detection DNA sequencing, DNA probes
• In many cases abnormalities in tumor suppressor
  genes

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Carcinogenesis

• 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)

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References
Carcinogenesis

• en.wikipedia.org/wiki/Carcinogenesis
• 4th year handouts
• Google.com
• ...