Smoking Cancer And The Environment Flashcards
Neoplasia
Autonomous or independent growth of an abnormal cell or tissue
Growth of which is more rapid than normal tissues and continues after the stimulus that initiated new growth is removed
Lifetime cancer risk
1 in 2
1 in 3 in developed world
What factors contribute to individuals cancer risk
Hereditary genetic factors
Environment/ lifestyle
Age
What is the development of tumours dictated by
Interaction between exogenous environmental factors endogenous process and host genetics
Environmental factors contributing to individuals cancer risk
Exposure to carcinogenic substances
Radiation
Oncogenic viruses
Lifestyle factors contributing to individuals cancer risk
Diet
Smoking
Weight
Exercise
Exogenous agents as sources of dna damage
Chemical
Radiation
Endogenous processes as sources of dna damage
Cellular metabolism
Replication stress
Spontaneous
Mutation drivers
Endogenous spontaneous
Exogenous induced
Endogenous spontaneous mutations
Errors in dna replication (dna polymerase)
Deaminatiom (cytosine to uracil)
Exogenous induced mutations
Exposure to endogenous carcinogens
Exposure to environmental carcinogens
Carcinogens reacting with dna to cause mutations
What is found in cigarette smoke and burnt toasts
Polycyclic aromatic hydrocarbons
Benzo a pyrene
Is a pro carcinogen
Activated by cytochrome p450
Mechanism of action of polycyclic aromatic hydrocarbons
Intercalates in DNA (forms bulky adducts)
-Covalently binds to Adenine and Guanine bases
-Leads to base pair changes in DNA
-Purine to pyrimidine transversion (Adenine to Thymine)
What do mutations in polycyclic aromatic hydrocarbons cause
Activation of proto oncogenes
Inactivate tsp
Uv mediated dna damage
Direct and indirect dna damage
Cross linking adjacent thymine bases
Prevents dna polymerase function
Ionising radiation definition
Radiation that Carries enough energy to free electrons from atoms or molecules thereby ionising them
Source of ionising radiation
X rays
Used in radiotherapy
Kill cancer cells
Exposure to ionising radiation
Leukaemia
Breast
Thyroid
Exposure to uv radiation
Basal cell carcinoma
Squamous cell carcinoma
Melanoma
Polycyclic hydrocarbons as an agent
Exposes in building fuel and dye industries
Skin lung and bladder cancer
Aromatic amines 2-napthylamine
Rubber and plastic industries
Bladder cancer
Benzene
Drugs plastic rubber and dye industries
Leukaemia
Asbestos
Construction of buildings and ships
Mesothelioma cancer
Mesothelioma
Malignant cells in the mesothelium linings around lungs abdomen and heart
Pleura peritoneum and pericardium respectively
Environment and lung cancer
Genetic predisposition to cancer
Xeroderma pigmentosum
Autosomal recessive inherited condition
Mutations inxeroderma pigmentosum genes, defect in NER
sensitivity to sunlight so 1000 fold significance incidence of skin cancers
HPV
Human papilloma virus
Benign warts
Cervical cancefx
Hepatitis b and c
Liver cancer.
EBV
Epstein Barr virus
Burkitt lymphoma
HIV
Kaposi sarcoma
HPV16
One of most common stds in young people
Higher in women
Biggest causative agent of cervical cancer and genital warts
Causes cancers by deregulating p53 and rb
HPV16 mechanism
Activating mutations to proto oncogenes
Ras
Raf
Myc
Inactivating mutations to tumour suppressor genes
APC (colorectal cancers)
CDK inhibitors e.g. wee1
P53 (master regulator)
Base excision repair BER
Removal of modified bases in the DNA
Nucleotide excision repair NER
Repairs bulky distortions in DNA
- Repairs polycyclic aromatic hydrocarbon adducts and UV cross links
- Key protein in repair pathway is xeroderma pigmentosum (XP)
DNA double stranded breaks
Most dangerous type of DNA damage
- Pathway 1: rapid Non-Homologous End Joining (NHEJ) and
- Pathway 2: slower Homologous Recombination Repair (HRR) involving BRCA
