Non-genotoxic carcinogenesis Flashcards
what is the most effective non-genotoxic carcinogens with implication for human health
fibrate drugs
what is auxotrophic
inability of an organism to synthesise a particular organic compound
what is the typical design of an AMES assay
Control Plate: spread ~ 100000000 his auxotrophs on a plate containing minimal medium, lacking histidine. Result: cells won’t grow, except for occasional revertant spontaneous mutant (at 1 in 10000000 rate, expect ~ 10 mutants/plate).
Experimental plate: spread same cells on similar plate, add a filter disk soaked in test chemical solution. If chemical is mutagenic, will diffuse into agar, will see increased number of mutants surrounding the disk
how is rat S9 liver microsome normally pre-treated prior to AMES assay
AhR activator (CYP1A1,CYP1A2 inducer)
what do fibrate drugs do and how doe they work
treat hyperlipidaemia
-act mainly by decreasing serum triglyceriders
- variable effects on LDL-Cholesterol
-can reduce the risk of coronary heart disease events in those with low HDL-cholesterol or with raised trigylcerides
Fibrates are first-line therapy only in those whose _. In type 2 diabetes, fenofibrate can be added to a statin for those _
- serum-triglyceride concentration is greater than 10mmol/litre or in those who cannot tolerate a statin.
- with a serum-triglyceride concentration exceeding 2.3mmol/litre, despite 6 months of treatment with a statin and optimal glycaemic control.
feeding rats and mice fibrate drugs results in =
100% liver tumour incidence by 1 year
what do fibrate drugs do to the rodent liver
- They make the liver enlarge – hypertrophy and hyperplasia.
- They cause peroxisome proliferation.
- They induce CYP4A enzymes
how is hyperplasia known to be an issue
BrdU (analogue of dT) is injected in animals hours before culling
you can look at tissue to determine incorporation of BrdU
if a cell is about to undergo division, cell will synthesied double the amount of DNA (uptake loads of Brdu)
What is BrdU
analogue of dT which is HRP conjugated
why is BrdU given hours before death
it will result in tumour which is harmful
how to determine amount of peroxisomes histological
peroxisomes are stained with the alkaline DAB method for cytochemcial localisation of catalase
what do peroxosomes
work with mitocondria in Beta fatty acid oxidation
gradually oxidised and removal of 2 carbon units (acetyl CoA) and fatty acid with 2 less carbons + NADH (ATP)
In only peroxisomes H2O2 is produced compared to H20 in mitocondria
what is fenton reaction
Fe2+ + H2O2 -> Fe3+ + OH + OH-
OH- is highly reactive
why do peroxisomes contain catalase
H2O2 -> 2H20 + O2 - stops OH- production
