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stephen.sturzenbaum@kcl.ac.uk

Yuzhi Chen

Yuzhi Chen

PROJECT:

Benzo[a]pyrene (BaP) is a highly carcinogenic environmental pollutant that can lead to genetic damage. To exert its carcinogenic properties, BaP needs to be bioactivated by members of the cytochrome P450 (CYP) superfamily which entail a large number of haem-containing mono-oxygenases. Activated intermediates can already lead to toxicity, but ultimately BaP-7,8-dihydrodiol-9,10-epoxide (BPDE) is the reactive metabolite capable of covalently binding to DNA forming adducts which further can cause mutations. Although BaP-induced DNA adduct formation is defined as the key process in cancer initiation in humans, the underlying mechanism by which BaP induces DNA damages in the nematode C. elegans still remains to be further explored. In my thesis, one key aim is to explore metabolic pathways of BaP bioactivation in C. elegans humanised for CYP1A1. Worms will be treated with BaP or reactive intermediates (e.g. BPDE) in order to bypass metabolic activation. Expression of CYPs will be assessed by qPCR and fluorescence microscopy. DNA adduct formation will be determined by 32P-postlabelling and/or mass spectrometry (e.g. formation of 8-oxoguanine). 

                                          

King's College London

  • Faculty of Life Sciences & Medicine
  • Analytical and Environmental Science Division
  • 150 Stamford Street
  • London
  • SE1 9NH

Funded by: