Team Gains Insights on How Bladder Cancer Is Linked to Smoking

May 08, 2020 | Biotechnology

Reading time: 2-3 minutes

Today’s Lab.Equipment Biotechnology news is sourced from Genetic Engineering and Biotechnology News (GEN):

Scientists from the University of York say they have recreated how toxins from smoking cause unique patterns of DNA damage. The discovery could help researchers better understand the cause of bladder cancer and the link to smoking, according to the university team. The causes of bladder cancer remain largely unknown, but smoking is seen as the main risk factor for the disease.

Simon Baker, PhD, from the department of biology, and his colleagues 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, which published its study “Procarcinogen Activation and Mutational Signatures Model the Initiation of Carcinogenesis in Human Urothelial Tissues In Vitro” in European Urology, analyzed all three billion letters of the genetic code to find a pattern of changes called a “mutational signature.”

“Disparity between genome-wide mutations in bladder and other cancers where smoking is a risk factor raises questions about carcinogenesis in different epithelia. To develop an experimental model of bladder carcinogenesis, we clonally expanded in vitro differentiated normal human urothelial (NHU) cells following exposure to an exemplar procarcinogen and used whole-genome DNA sequencing to derive mutational signatures. Benzo[a]pyrene (BaP) was activated by endogenous cytochrome P450 (cytochrome P450 family 1 subfamily A member 1 [CYP1A1]) to create genomically modified NHU cells. Comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) showed that mutations induced by BaP in NHU cells were similar to smoking-associated signatures in bladder and other cancers, including single- and doublet-base substitution signatures characterized by C > A transversions (COSMIC_SBS4 and COSMIC_DBS2, respectively), and an insertion/deletion signature of C deletions in homopolymer... Want to read more? Visit the GEN – Genetic Engineering and Biotechnology News​ Blog.

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