CARCINOGENESIS Niko Blaevi Mentor A mega Horvat Definition

CARCINOGENESIS Niko Blažević Mentor: A. Žmegač Horvat

Definition Carcinog enesis The process of transformation from a normal cell to a cancerous one Synonym: neoplasia

Neoplasia Carcinog enesis 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

Carcinog enesis NORMAL CELL growth factor receptor cytoplasm signal transduction nucleus activation of transcription DNA RNA

Carcinog enesis NEOPLASTIC (malignant) CELLS Increase in growth factors Increase in growth factor receptors Increase in signal transduction - Disturbed processes of mitosis and protein synthesis Increase in activation of transcription

Carcinog enesis Malignant cells Continuous reproduction Formation of abnormal proteins ANAPLASIA: ▪ ▪ ▪ loss of normal cell function (abnormal DNA transcription) proliferation movement of cells Caused by altered DNA and altered invasion of nearby tissue cellular programs which make new metastasis signals

Carcinog enesis Hypotesis of the origin of neoplasia 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

Regulatory genes Carcinog enesis 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 p 53

Carcinog enesis 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

Causes Environmental agents Heredity Carcinog enesis

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

Environmental agents Carcinog enesis 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 – Burkitt lymphoma Two types – RNA and DNA viruses Carcinog enesis

Heredity Carcinog enesis 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

Carcinog enesis 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)

References en. wikipedia. org/wiki/Carcinogenesis 4 th year handouts Google. com. . . Carcinog enesis