Increased cancer risk of augmentation cystoplasty

Possible role for hyperosmolal microenvironment on DNA damage recognition

Bradley P. Dixon, Albert Chu, Jeff Henry, Rebecca Kim, John Bissler

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Patients who have had surgical bladder augmentation have an increased risk of bladder malignancy, though the mechanism for this increased risk is unknown. Hyperosmolal microenvironments such as the bladder may impair DNA damage signaling and repair; this effect may be more pronounced in tissues not normally exposed to such conditions. Comparing gastric and colon epithelial cell lines to transitional epithelial cell lines gradually adapted to an osmolality of 600 mOsm/kg with either sodium chloride or urea, cell lines of gastrointestinal origin were inhibited in their ability to activate ATM and downstream effectors of DNA damage signaling and repair such as p53, Nbs1, replication protein A (RPA), and γH2AX following the induction of DNA damage with etoposide. In contrast, bladder cell lines demonstrated a preserved ability to phosphorylate ATM and its effectors under conditions of hyperosmolal urea, and to a lesser extent with sodium chloride. The bladder cell lines' ability to respond to DNA damage under hyperosmolal conditions may be due in part to protective mechanisms such as the accumulation of intracellular organic osmolytes and the uroplakin-containing asymmetric unit membrane as found in transitional epithelial cells, but not in gastrointestinal cells. Failure of such protective adaptations in the tissues used for augmentation cystoplasties may place these tissues at increased risk for malignancy.

Original languageEnglish (US)
Pages (from-to)88-95
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume670
Issue number1-2
DOIs
StatePublished - Nov 2 2009

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DNA Damage
Urinary Bladder
Cell Line
Epithelial Cells
Neoplasms
Sodium Chloride
DNA Repair
Urea
Uroplakins
Replication Protein A
Etoposide
Osmolar Concentration
Stomach
Colon
Membranes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis

Cite this

Increased cancer risk of augmentation cystoplasty : Possible role for hyperosmolal microenvironment on DNA damage recognition. / Dixon, Bradley P.; Chu, Albert; Henry, Jeff; Kim, Rebecca; Bissler, John.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 670, No. 1-2, 02.11.2009, p. 88-95.

Research output: Contribution to journalArticle

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