Being able to work with normal urothelium provides an ideal system for investigating the beginning of cancer initiation through exposure to mutagens and non-genotoxic carcinogens. Alternatively it also provides a useful experimental system to explore sensitivity of urothelial cells to candidate therapies.
Different cancers can have different levels of somatic mutations, bladder cancer comes behind only melanoma and lung cancer. The high mutational rate in bladder cancer suggests direct contact with urinary mutagens is an important part about what causes the disease.
The bladder already has a range of defences to try and stop cancer occurring. One of these is cytochrome P450 (CYP) enzymes, which is not fully understood. The JBU has started looking at the role of CYP enzymes and their potential therapeutic targets.
Many compounds which cause bladder cancer are pro-carcinogens and do not cause cancer until they have been activated by endogenous enzymes. For a long time this was believed to have occurred in the liver. At beginning to 2018, the JBU published first in human evidence that cytochrome P450 enzymes can activate carcinogens locally in the bladder urothelium.
The bladder is the site of a number of poorly understood, chronic, benign syndromes that do not attract significant research funding and affect individuals all their life. The JBU has various studies into the benign dysfunctional area which has emerged as a result of the in vitro models of human urothelium. These include:
Mutagens - an agent, such as radiation or a chemical substance, which causes genetic mutation
Non-genotoxic carcinogens - a chemical capable of producing cancer by some secondary mechanism not related to direct gene damage.
Endogenous - Enzymes secreted by the animal cell itself