CREDIT: PHIL ROBERTS

Researchers from the University of York have recreated how toxins from
smoking cause unique patterns of DNA damage. The discovery could help
scientists better understand the cause of bladder cancer and the link
to smoking.

The causes of bladder cancer remain largely unknown, however smoking
is seen as the main risk factor for the disease.

Researchers – led by Dr Simon Baker from the Department of Biology –
grew human bladder tissues in the laboratory and exposed them to a
common toxin from cigarette smoke. After the tissues were damaged by
the smoke toxin, the team analysed all three billion letters of the
genetic code (DNA) to find a pattern of changes called a “mutational
signature.”

Dr Baker said: “Mutational signatures can be used like fingerprints at
a crime scene. When we look at the DNA in a cancer we can see the
fingerprints of all the criminals involved in causing the damage that
led to cancer.

“The DNA damaging event might be exposure to cigarette smoke or UV
from the sun but it might also be an unknown event that causes
cancer.”

“Our study found that the smoke toxin left its distinctive
fingerprints on the DNA of bladder tissues grown in the laboratory.
However, when we looked at the DNA of patients’ bladder cancers the
mutational signature, of the smoke toxin, was only responsible for a
small amount of the damage.

“So despite smoking being the key risk factor for bladder cancer,
direct damage of the DNA by smoke toxins is unlikely to be the main
reason for these cancers forming.”

It may be that the smoke toxins accelerate other DNA damaging events
and attention is now focussing on a family of enzymes called “APOBEC”.

APOBEC enzymes destroy viruses by mutating their DNA as part of the
body’s natural defences against infection, but recent studies suggest
they might mistakenly target our own DNA in a number of cancer types.
The next stage of the study will be to try and understand how and why
APOBEC enzymes become activated in the cells of the bladder.

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The paper, “Procarcinogen Activation and Mutational Signatures Model
the 4 Initiation of Carcinogenesis in Human Urothelial Tissues In
Vitro” is published in European Urology