Mutagens - chemical or physical and causes DNAdamage. Mutagens increasemutation rate in DNA. Causes cancer. Also can be carcinogens.
Carcinogens can damage DNA causing cancer. Cancer cells have mutatedprotooncogenes that causes too much cellgrowth.Tumorsuppressorgenes are inactivated causing uncontrolled cell growth.
Carcinogenesis – has 4 stages: initiation – promotion – conversion and progression.
Initiation – damaged DNA leads to mutations due to mutagens.
Promotion – altered cells replicate fast and increasing in number
Progression – leads to invasion as cells become more aggressive and mutate further.
Direct carcinogens – bind directly to DNA forming DNA adducts that leads to mutation
Procarcinogens – need to be metabolically activated to cause DNAdamage.Procarcinogens to proximatecarcinogens to ultimatecarcinogens.
Mutagens and carcinogens damage DNA by adduct formation, alkylation, deamination, dimerization and oxidative damage.
Bulky aromatic adducts – large molecules formed when chemicals bind DNA. Formed due to incompelte combustion of fossil fuels. Is chemically inactive but need cytochrome P450 to be harmful.
Aflatoxin B1 – they are toxins formed by certain moulds that are toxic and can lead to liver cancer and cirrhosis. They are procarcinogens that cause DNA damage by binding to guanine.
Alkylating agents – small alkyl groups that are added to specific parts of DNA (bases) causing adducts. This start as procarcinogens. Some adducts can cause mutations which can lead to instability which results in DNA base loss.
Deaminating agents – chemicals that remove amino group from certain DNA bases leading to them to convert from one form to another. This can cause a DNA mismatch which can lead to DNA replicationerror and then mutations
There are 4 types of repair mechansims – excision repair (errorremoval due to oxidative and adduct damage), mismatch (deamination and insertiondamageremoval), single strand break and direct reversal (methylgroupremoval without baseremoval)
Base exicision repair – fixes DNA base damage due to deamination and methylation.8–oxo- guanine is DNA base damage due to reactive oxygen and DNA glycosylase removes damaged base forming an abasicsite.Polymerase, endonuclease and ligase fix the gap and maintain the DNA integrity.
Nucleotide excision repair – DNA damage is recognised and removed. DNA polyemerase fills gap by using nucleotides.Ligase fills gap and keeps the DNA structure.