The process of transformation from a normal cell to a cancerous one
Synonym: 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
Carcinogenesis
NORMAL CELLgrowth factorgrowth factor receptor
signal transduction
activation of transcription
cytoplasm
nucleusDNA
RNA
Carcinogenesis
NEOPLASTIC (malignant) CELLS
Increasein growth factors
Increasein growth factorreceptors
Increase in signal transduction
Increase in activation of transcription
- Disturbed processes of mitosis and protein synthesis
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
Carcinogenesis
Caused by altered DNA and altered cellular programs which make new signals
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
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
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 --> become clinical cancers
Carcinogenesis
Chemical carcinogens: hydrocarbons (cigarette smoke, pipe smoke, automobile
exhaust gases) insecticides dyes industrial chemicals insulation hormones
E.g. - DES (diethylstilbestrol) - estrogen drugs
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
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
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
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)
Carcinogenesis