Chemical carcinogens Flashcards
what is 3,4-benzypyrene oxidised by and to
glutathione s-transferases to 7,8-epoxide metabolite
where is p53 highly active
malignant cells
what does error-prone DNA replication require
DNA polymerases delta and epsilon
Which cytochromes biotransforms polycyclic aromatic hydrocarbons (4)
- P450
- 1A1
- 1A2
- 1B1
what is the formation of epoxides catalysed by
UDP-dependent glycuronosyl transferases
what is the chemically structure of polycyclic aromatic hydrocarbons
carbon and hydrogen arranged into aromatic rings
what do all major carcinogens in this group contain
bay region
what does the K region contain
higher electron density
what is a imbalance between K and L regions suggested to cause
carcinogenicity
what can epoxides form
K regions
what occurs during nucleotide excision repair
repairing of DNA damage with low fidelity
where are polycyclic aromatic hydrocarbons in the environment from
anthropogenic sources
where is the aryl hydrocarbon receptor found
nucleus of hepatocytes
what excretes polycyclic aromatic hydrocarbons
kidneys
what do the bay regions bind with in particular
NH2 group of guanine
what kind of molecules are PAHs
planar molecules
what do most PAHs contain
phenanthrene nucleus
where in the plenanthrene moiety is the bay region located
C4 to C6
what increases carcinogenicity
addition of other planar ring systems to C6C7
two types of cancer
benign and malignant
three most common classifications of cancer and where do they develop
- carcinomas - epithelial cells
- sarcomas - bone and muscle
- leukaemia - blood
five classes of chemical carcinogens
- alkylating agents
- nitroso compounds
- azo dyes
- aromatic amines
- polycyclic aromatic hydrocarbons (PAHs)
when are PAHs generated
whenever organic materials are burned
when was the association between cancer and PAHs first noted
in 1775
what do the diol-epoxides of 3,4-benzypyrene normally bind to?
guanine residues of DNA
what correlations were found between carcinogenic activity and electron density
high electron density resulted in greater carcinogenic activity
what do PAHs form and what is this reaction catalysed by?
K-region epoxides catalysed by cytochrome p450
why are epoxides dangerous?
they react directly with DNA forming mutagens and carcinogenic activity
what became clear by the 1970s regarding epoxides
that non-K-region exoxides could exist
how do the diol-epixodes of 3,4-benzpryene bind to guanine
covalent bond is formed between C10 of benzo(a)pyrene and the exocyclic 2-amino
why does binding of PAH cause damage to DNA
repair is not always accurate leading to point mutations
what do 10% of human tumours contain
mutations of ras genes
what is different about oncogenic p21
it has lost its GTPase activity = constant signalling for growth
how to measure PAH exposure
electrophilic metabolites of PAHs form covalent adducts with albumin and haemoglobin which can then be assayed
