Niko BlaževićMentor: A. Žmegač Horvat

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

Environmental agents

Heredity

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

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Carcinogenesis