title: Biosafety of in vivo adenovirus-p53 intravesical administration in mice.
abstract: OBJECTIVE
  To evaluate the biosafety and in vivo biodistribution of intravesical instillation of an adenovirus that contains human p53 gene. Mutations of p53, which are found in as many as 40% of transitional cell carcinomas, are associated with a poor prognosis and resistance to chemotherapy and radiation therapy. Restoration of wild-type p53 status by means of adenoviral-mediated therapy may enhance apoptosis and improve the response to therapy, but the issues of biosafety and toxicity have not yet been addressed.
  
  
  METHODS
  Adenovirus-p53 (1 x 10(8), 1 x 10(9), and 5 x 10(9) pfu/mL) and luciferase reporter gene (5 x 10(9)) were instilled into the bladders of anesthetized female BALB/c mice. The mice were killed on days 1, 3, 6, and 13, and representative samples of the bladder, ureter, kidney, adrenal gland, ovary, liver, heart, and lung were removed for histologic evaluation.
  
  
  RESULTS
  No histologic signs of toxicity were found. The hematologic and biochemical profiles of the mice were normal, with the exception of a transient elevation in liver function tests on day 1 in the three treatment groups.
  
  
  CONCLUSIONS
  Intravesical instillation of adenovirus-p53 was well tolerated; the bladder urothelium appeared to prevent systemic dissemination. The results of these experiments support the safety of intravesical gene transfer by intravesical instillation.
authors.affiliation: Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: P
authors.initials: P
authors.lastname: Perrotte
authors.forename: M
authors.initials: M
authors.lastname: Wood
authors.forename: J W
authors.initials: JW
authors.lastname: Slaton
authors.forename: D R
authors.initials: DR
authors.lastname: Wilson
authors.forename: L
authors.initials: L
authors.lastname: Pagliaro
authors.forename: R E
authors.initials: RE
authors.lastname: Price
authors.forename: C P
authors.initials: CP
authors.lastname: Dinney
mesh_terms: D000256:Adenoviridae / Q000201:enzymology / Q000302:isolation & purification; D000283:Administration, Intravesical; D000818:Animals; D005260:Female; D016158:Genes, p53; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C / Q000097:blood
chemical_list: D008156:Luciferases