title: Validation of an HPV16-mediated carcinogenesis mouse model.
abstract: OBJECTIVE
  Human papillomavirus Type 16 (HPV16) infection is a necessary but alone insufficient cause of invasive cervical cancer (ICC) and likely causes other genital cancers. Individual genetic variability influences the natural history of the neoplasm. Developing a variety of animal models to investigate HPV16-mediated carcinogenesis is important to Phase 1 trials for human cancer treatments.
  
  
  METHODS
  C57BL/6 mice expressing the HPV16-E7 transgene were treated with 100 nmoles of 7,12-dimethylbenz(a)anthracene (DMBA) on dorsal-thoracolumbar skin for ≤20 weeks.
  
  
  RESULTS
  Transgenic-HPV16E7 mice showed more tumors (14.11±1.49 vs. 7.2±0.73) that more quickly reached maximal size (17.53±0.53 vs. 28.75±0.67 weeks) than syngeneic controls.
  
  
  CONCLUSIONS
  DMBA topically-treated C57BL/6-HPV16E7 mice developed chronic inflammation as well as benign and malignant lesions, many of which ulcerated. Histology showed that the HPV16-E7 transgene more than doubled the effect of complete carcinogenesis against a C57BL/6 background alone, strongly influencing the number, size, and time-to-maximal tumor burden for DMBA-exposed transgenic-C57BL/6 mice.
authors.affiliation: Division of Translational Sciences, School of Nursing, University of California at Los Angeles (UCLA), Los Angeles, CA, U.S.A.
authors.forename: Katherine
authors.initials: K
authors.lastname: De Azambuja
authors.affiliation: Division of Translational Sciences, School of Nursing, University of California at Los Angeles (UCLA), Los Angeles, CA, U.S.A.
authors.forename: Provabati
authors.initials: P
authors.lastname: Barman
authors.affiliation: Division of Translational Sciences, School of Nursing, University of California at Los Angeles (UCLA), Los Angeles, CA, U.S.A.
authors.forename: Joy
authors.initials: J
authors.lastname: Toyama
authors.affiliation: Division of General Internal Medicine and Health Services Research and David Geffen School of Medicine at UCLA, Los Angeles, CA, U.S.A.
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.affiliation: Department of Laboratory Animal Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, U.S.A.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Lawson
authors.affiliation: Department of Laboratory Animal Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, U.S.A.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Williams
authors.affiliation: Division of Translational Sciences, School of Nursing, University of California at Los Angeles (UCLA), Los Angeles, CA, U.S.A.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Chua
authors.affiliation: Division of Translational Sciences, School of Nursing, University of California at Los Angeles (UCLA), Los Angeles, CA, U.S.A.
authors.forename: Deborah
authors.initials: D
authors.lastname: Lee
authors.affiliation: Teagasc Food Research Centre, Moorepark, Fermoy, Ireland.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Kehoe
authors.affiliation: Teagasc Food Research Centre, Moorepark, Fermoy, Ireland.
authors.forename: Andre
authors.initials: A
authors.lastname: Brodkorb
authors.affiliation: Center of Comparative Medicine, Baylor College of Medicine, Houston, TX, U.S.A.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schwiebert
authors.affiliation: UCLA Department of Medicine, Hematology/Oncology, Los Angeles, CA, U.S.A.
authors.forename: Scott
authors.initials: S
authors.lastname: Kitchen
authors.affiliation: Division of Translational Sciences, School of Nursing, University of California at Los Angeles (UCLA), Los Angeles, CA, U.S.A.
authors.forename: Aamir
authors.initials: A
authors.lastname: Bhimani
authors.affiliation: Division of Translational Sciences, School of Nursing, University of California at Los Angeles (UCLA), Los Angeles, CA, U.S.A. dwiley@ucla.edu.
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Wiley
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D001706:Biopsy; D002273:Carcinogens / Q000008:administration & dosage; D002472:Cell Transformation, Viral; D004195:Disease Models, Animal; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications*; D047368:Tumor Burden
chemical_list: D002273:Carcinogens; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D015127:9,10-Dimethyl-1,2-benzanthracene
keywords: 7,12-dimethylbenz(a)anthracene (DMBA); HPV type 16 (HPV16); HPV16E7; mice; transgenic