Carcinogens And Metaplasia

Question 0

Examples of chemical carcinogens

Answer 0

Polycyclic hydrocarbons-> cigarette smoke-> lung cancer
Aromatic amines-> industrial exposure-> con tend to active agents in the liver-> concentrated during excretion-> urothelium cancers
Nitrosamines-> effect gut bacteria
Alkylation agents-> bind DNA so are directly mutagenic-> used in chemo-> treating one cancer but increasing the chance of another

Question 1

Chemical carcinogens types

Answer 1

Genotoxic-> direct DNA damage by adding things to it
Mitogenic-> bind cell receptors and stimulate cell division
Cytotoxic-> produce tissue damage leading to hyperplasia
Direct acting-> can directly cause neoplasia
Procarcinogens-> agent requires conversion to an active carcinogen
Initiating agents-> don’t directly cause neoplasia but cause genetic abnormality that predisposes it
Promoting agents-> prolonged exposure causes development of neoplasia-> increased cell turnover

Question 2

Stages of chemical carcinogensis

Answer 2

1) initiation-> induction of genetic changes
2) promotion-> induction of cell proliferation
3) progression-> persistent cell proliferation causes secondary genetic abnormalities-> lead to dysregulation and then autonomous cell growth

Question 3

Physical carcinogens

Answer 3

Irradiation-> direct DNA damage, potent-> DNA breaks and instability
-x rays-> bone marrow and exposed skin
-inhalation of radioactive dust/gas
-ingestion of radioactive iodine-> thyroid
-incorporation of radioactive metals into bone
-UV
Asbestos-> potent when inhaled-> irritates lungs causing increased cell proliferation-> increased risk of neoplasia

Question 4

Viral carcinogens

Answer 4

Epstein Barr-> burkits lymphoma, nasopharyngeal carcinoma, other B cell lymphoma, some Hodgkin's
Hep B-> hepatocellular 
HPV> cervical and some skin carcinomas
HTLV-> T cell leukaemia/lymphoma 
HSV8-> kaposi sarcoma-> systemic

Question 5

Common cytogenic abnormalities in tumours

Answer 5

Gain or loss of chromosomes
Deletion of chromosomes
Inversion
Translocation
Selective amplification
Chronic myeloid leukaemia-> fusion of oncogene bar-abl-> protien with tyrosine kinase activity
Follicular lymphoma-> IgH gene from chr 14 fused to Bcl-2 gene on chr 2-> prevention of apoptosis
Ewing’s sarcoma-> fusion of LFT-1 with EWS gene-> protein with high transcriptor activity
Neuronalblastoma-> amplification of n-myc
Burkits lymphoma-> fusion of c-myc with IgH-> c-myc expression

Question 6

Pre neoplastic conditions

Answer 6

Some non-neoplastic diseases carry increased risk of later development of neoplasia
Hyperplasia can result in dysplasia-> progress to carcinoma
Endometrial layers, breast lobules
Chronic gastritis
Hepatic cirrhosis
Celiac disease
Autoimmune thyroiditis

Question 7

Inherited neoplastic conditions

Answer 7

MEN syndrome-> chr 10+11 mutation-> multiple tumours in endocrine organs
Polyposis coli-> absent AP-> adenoma tag and carcinomas of colon
Li-fraumeni-> mutated p53-> breast and sarcomas
Xeroderma pigmentosum-> abnormal DNA repair
Neurofibromatosis type 1-> abnormal NF1-> benign and malignant tumours of peripheral nerves

Question 8

Immune responses and tumour biology

Answer 8

Tumours specific antigens:
Present only in tumour cells
Lymphoid infiltrate in some tumours suggests thee is an immune response to these antigens-> patients who have lymphoid infiltrate have a better prognosis 
Vaccines against antigens? 
Tumours associated antigens:
Present on both tumour and normal cells
Anfectal antigens-> normally expressed in bone development but are r expressed in neoplastic cells 
AFP expressed in hepatocellular cancer
CEA in gastrointestinal cancer