Carcinogenesis Flashcards
What is a carcinogen?
a substance capable of causing cancer in living tissue.
Quickly describe the mechanism of chemical carcinogenesis
Initiation, promotion (reversible), progression (irreversible) and malignancy
What is initiation?
An initiation/mutagenic event involving cellular genome mutations in tumour suppressor genes and oncogenes
What is the promotion (reverable) step involving?
This stimulates proliferation in both normal and mutated cells
What is the progression (irreversible) step involving?
Irreversible enhancement/repression of gene expression. Selection of neoplastic cells for optimal growth
What is the latent period
The time between exposure to carcinogen and the first occurrence of tumour developing
Outline the mechanisms of cancer induction in the bladder by napthylamine
The liver converts 2-naphthylamine (2NTA) into a carcinogenic metabolite (2-amino-naphthol) which is then detoxified to glucuronide and excreted by the kidneys. In the bladder the urothelial cells express beta-glucuronidase which converts glucuronide into a carcinogen.
What tumour does asbestos induce?
Mesothelioma. It is a bulky tumour that can fill the chest cavity, metastasis is uncommon.
Benzopyrene causes mutations in what genes? This is evidence smoking causes cancers
K-Ras and p53 which are the two genes most commonly mutated in smoking related lung cancers.
Describe the metabolism of benzo(a)pyrene
This is the main carcinogen of tobacco. It is converted by AHH into Benzo(a)pyrene diol epoxide which binds to DNA forming damaging adducts
What detoxifies carcinogens?
GSTM1 so if this is not expressed people have an increased risk of developing lung and bladder cancers
What tumours does benzpyrene induce?
lung, bladder, oesophagus, kidney and pancreas cancers
What evidence supports that passive cancer can cause cancers
Children with a mother or family member who smoke have higher plasma levels of tobacco smoke metabolites
What tumour can aflatoxins induce?
Liver cancers.
Why are there fewer cancers found in the small intestine compared to the large intestines?
Bcl2 is expressed in the large intestine but not in the small intestines. Bcl2 protects damaged cells from dying and therefore cells survive and accumulate mutations leading to tumour formation.
