Flashcards in carcinogenesis Deck (86)
what are lab experiments done on?
rodents, human cells and bacteria
what are two types of unavoidable exposure?
occupational due to carcinogenic agents such as heavy metals cadmium and nickel, and accidental exposure
how would you identify geographical variation in risk?
study migrant populations - shows that environment can play a significant role in rates of cancer as there are enormous variation in the incidence of specific cancers in one part of world to another
what does mining of hematite and uranium expose workers to?
what has a high prevalence among woodworkers?
paranasal sinuses and sinonasal cavities cancer
what is high in boot manufacture and leather dust exposure occupations?
what is EPIC?
it is the european prospective investigation into cancer and nutrition and is to investigate lifestyles etc and the incidence of cancer and other chronic disease
what are the categories of human carcinogens and an example?
chemicals (PAHs), radiation (radon), infectious agents (HPV), minerals (asbestos) and physiological (oestrogen)
how can human carcinogens lead to cancer?
prolonged exposure can lead to an accumulation of genetic alteration in clonal populations of cells
what are PAHs?
polycyclic aromatic hydrocarbons - class of chemical agent that is produced when organic matter is burnt
what are nitrosamines?
class of chemical agent that are produced in diet when amino acids have a nitrogen group attached to them which are then converted to carcinogenic agents
what does aflatoxin, alcohol and asbestos target?
alcohol - liver, larynx, pharynx, oesophagus
asbestos - lung pleura
what odes tobacco smoke, UV and HPV target?
tobacco smoke - mouth, lung and oesophagus
HPV - liver
UV - skin
what does HCV, oestrogen and X rays target?
HCV - pancreas, kidneys, bladder
oestrogen - breast
X rays - bone marrow resulting in leukaemia
what is a carcinogen?
any agent that significantly increases the risk of developing cancer
what does genotoxic mean?
it is a carcinogen that can chemically modify or damage DNA i.e. is an initiator
what is a complete carcinogen?
one that can initiate and promote e.g. UV light
what is a non - genotoxic carcinogen?
on that induces proliferation and DNA replication i.e. is a promoter
what is the difference between oestrogen and ROS?
they are both non-genotoxic carcinogens, however oestrogen will induce proliferation as it's normal physiological function, whereas reactive oxygen species (free radicals) will lead to proliferation through the replacement of dead or damaged cells so are cytotoxic
what does mutation induction require?
initiation requires chemical modification of DNA and replication of the modified DNA and misincorporation by DNA polymerase
how is misincorporation possible?
DNA replication is not error free so that evolution can occur. DNA polymerase makes mistakes at a very low rate but this is significant as it results in accumulation of genetic variation or polymorphisms in coding and non coding region of genome - can be deleterious - mutations
what increases the risk of point mutations/misincorporation?
the presence of a modification (miscoding or on coding adducts or lesions) in the DNA
what else can these modifications result in?
cause the polymerase to stall - double stranded break in DNA which is a target for deletions, translocations or insertions
how can chemical modification occur?
environmental insult or endogenous reactive molecules e.g. free radicals produced by normal physiological processes
what do good promoters to for carcinogenesis?
they stimulate the two rounds of DNA replication that is required for mutation fixation
they stimulate clonal expansion mutated cells which enables the accumulation of further mutations
how will a papilloma progress to a carcinoma?
further rounds of mutations and clonal expansions
progression is also known as persistence
what is the link between cell division and cancer?
the lifetime risk of cancer in certain tissues and the number of stem cell divisions over a lifetime in these tissues has a very strong correlation
what is a point mutation?
a base pair substitution
it is the smallest change in DNA sequence that can give rise to a change in DNA function
they can results in missense or nonsense / truncated protein
this can overactivate or underactivate the protein
which mutation usually results in a inactive protein?
frameshift - where there is a gain or loss of one or several base pairs meaning that downstream the reading frame is different