Carcinogenesis Flashcards
what is initiation?
+ mutagenic
+ cellular genome mutations in tumour suppressor genes and oncogenes
what is a carcinogen?
A substance or agent that can cause cells to become cancerous by altering their genetic structure
what is promotion (acceleration)?
+ reversible, not mutagenic
+ stimulates proliferation and causes both mutated and normal cells to proliferate
e.g TPA (phorbol esters), dioxin (polycyclic aromatic compounds)
what is progression?
+ irreversible enhancement/repression of gene expression
+ selection of neoplastic cells for optimal growth genotype/phenotype in response to cellular environment
what is the latent period?
the amount of time that elapses between initial exposure and diagnosis of cancer
what cancer is 3,4-benzpyrene associated with?
scrotal cancer
which carcinogenic substance is associated with scrotal cancer?
3,4-benzpyrene
what carcinogenic substance was associated with bladder cancer?
2-napthylamine (2NTA)
what cancer is 2-napthylamine (2NTA) associated with?
bladder cancer
describe the mechanism of cancer induction in the liver by napthylamine?
+ liver converts 2NTA to carcinogenic metabolite 2-amino-naphthol
+ detoxified to glucuronide (not carcinogenic)
+ excreted by kidneys
describe the mechanism of cancer induction in the bladder by napthylamine?
+ human urothelial cells express β-glucuronidase
+ converts glucuronide to a carcinogen
what form of cancer is associated with asbestos?
+ bronchiogenic carcinomas
+ ‘blue’ asbestos fibres: mesothelioma
what type of substance is asbestos?
fibrous silicate
what are features of the mesothelioma from asbestos?
+ dense white sheet
+ metastatic spread uncommon
+ bulky tumour that can fill chest cavity
what are the two genes more frequently mutated in smoking-related lung cancers?
K-Ras and p53 (guanine mutations-misread as thymine)
what is the active carcinogen in tobacco smoke?
3,4-benzpyrene (benzopyrene)
what is the role of AHH in cancer?
converts benzopyrene into benzopyrene diol epoxide which binds to DNA forming damaging products
which protein can detoxify carcinogens?
GSTM1 (glutathione S transferase)
smoking increases the risk of which other cancers?
+ oesophagus
+ bladder
+ kidney
+ pancreas
describe the sources of carcinogens in diet (NITRITES AND NITRATES)?
+ in food additives and fertilisers that enter drinking water
+ gut bacteria converts nitrites and nitrates
+ nitrosamines produced - carcinogens that can lead to GI tract and liver cancers
what cancer are aflatoxins (aflatoxin B1) associated with?
liver carcinomas
why are there much higher incidences of tumours in large intestine than small intestine?
+ Bcl2 expresses in colonic epithelium
+ Bcl2 not expressed in small intestine
+ Bcl2 suppresses apoptosis therefore damaged cells survive, mutate and lead to carcinogenesis
what type of UV radiation causes carcinogenesis?
non-ionising (causes excitation of atoms)
which individuals are particularly at risk of UV-induced damage?
repair deficient individuals: xeroderma pigmentosum - rare autosomal recessive disease
what is xeroderma pigmentosum?
+ inherited deficiency of endonuclease (enzyme in pathway of thymine dimer removal)
+ children show severe skin abnormalities (freckling, multiple squamous and basal cell carcinomas and melanomas)
+ requires protection from sunlight
what types of cancer is associated with ionising radiation?
+ skin (x-ray)
+ leukaemia (thermal and ionising)
+ bone (radium)
