MOD 20 - carcinogenesis: causes of cancer Flashcards
what are the different categories of human carcinogens
chemical, infectious agent , radiation, minerals, physiological, chronic inflammation
what cancer does aflatoxin cause?
liver cancer - aflatoxin produced from mould found on corn etc
what cancer does alcohol cause?
pharynx, larynx, oesoph, liver
what does asbestos cause
lung pleura - eventually cause lung cancer
what cancer does X-ray cause
bone marrow (leukaemia)
what cancer does UV light cause
skin
what cancer does oestrogen cause
breast
what cancer does tobacco cause?
mouth, lung, oesophagus,
pancreas, kidney, bladder, etc.
what cancer does HBV cause
liver
What cancer does HPV cause?
cervix
definition of carcinogen?
any agent which significantly increases the risk of developing cancer
definition of initiators in terms of cancer?
carcinogen which chemically modify or damage DNA
definition of promoters in terms of cancer?
carcinogens which induce proliferation and DNA replication
what is a complete carcinogen
a carcinogen which can initiate and promote
what does initiation of mutation requires
chemical modification of DNA, replication of moditfied DNA and mis-incorporation by DNA polymerase
why are promotors important?
1 - they can stimulate DNA replication required for mutation fixation
2- they can stimulate clonal expansion of mutated cells which enables the accumulation of further mutations
how does initiation, promotion and progression lead to cancer?
genotoxic initiating agent damages DNA
promoting agent fixes damage as a mutation and converts normal cell into mutant initiated cells
promoting agent stimulates clonal expansion of initated cell to produce benign cancer
further rounds of mutations and clonal expansion allows benign cancer to progress to carcinoma
what are some common genetic abnormalities which have potential to cause a tumour?
base pair substitution, frameshift, deletion, gene amplification, chromosomal translocation, chromosomal inversion, aneuploidy (the presence of an abnormal number of chromosomes in a cell)
how is a section of a gene being switched off
methylation of the CpG islands in the promoter sequences
how does tumour cells cause the switching off of the tumour suppresser genes
by causing malfunction of the methylation of the CpG island in the promoter region of the tumour suppressor genes and so they are switched off
what is the most common way of causing the tumour suppressor genes to switch off?
aberrent methylation of gene promoters - leads to epigenetic inactivation of the tumour suppressor genes
what is oncogenes
genes which has the potential to cause cancer
what does mutation of the oncogenes lead to?
gain of function - Base pair substitutions, amplification, translocations, inversions
what does mutation of the tumour suppressor gene lead to?
loss of function - Base pair substitutions, frameshifts, deletions, insertions, chromosomal rearrangements, chromosome loss, promoter methylation
which one of all the genetic mutation will cause activation of the genes
amplification
what is direct acting carcinogens
interact directly with DNA, e.g. oxygen radicals, nitrosomines, UV light, ionising radiation
what is procarcinogens carcinogens
require enzymatic (metabolic) activation before they react with DNA, e.g. aromatic amines, polycyclic aromatic hydrocarbons (PAHs)
how is benzopyrene produced?
through combustion of most organic material such as meat, tobacco and fuel
what type of carcinogen is benzopyrene
pro-carcinogen
which enzyme is required in the transformation of benzopyrene
P459 mixed function oxidase
what chemical will benzopyrene be turned into
BPDE
how does BPDE work?
react with TP53
how is the normal genes be protected?
repair process
base - excision repair
nucleotide - excision repair
recombinational repair
mismatch repair
which repair process is malfunctioning for HNPCC
mismatch repair
what are some of the defence against carcinogenesis
- dietary antioxidants, -detoxification -mechanisms
- DNA repair enzymes
- apoptotic response to unrepaired genetic damage
- immune response to infection and abnormal cells
what is benzopyrene presence in?
tobacco smoke
what can alcohol be converted into which can cause DNA damage
acetaldehyde
what can alcohol do to the body in order to produce cancer
- incr oestrogen and testosterone
- incr carcinogenic chemical uptake into cells in upper GI
- redu lev of folate needed for accurate DNA replication
- can kill surface epithelium leading to unscheduled proliferation
what can oestrogens casuse
stimulate cell division and induce DNA damages
