title: 3,3'-Diindolylmethane increases serum interferon-γ levels in the K14-HPV16 transgenic mouse model for cervical cancer.
abstract: While cervical cancer incidence and mortality rates have declined in the United States, this cancer represents a worldwide threat. Human papilloma viral infection causes cervical neoplasia (CIN). 3,3'-Diindolylmethane (DIM) prevents or inhibits the progression from cervical dysplasia to cancer. The aim of this study is to determine the most effective dose of DIM given continuously in food, that significantly increases serum interferon gamma levels (IFN-γ) in the K14-HPV16 transgenic mouse model for cervical cancer.
  
  
  METHODS
  Five doses of DIM in food were administered to the mouse model for 20 weeks. Serum Interferon gamma (IFN-γ) levels and estrogen metabolite levels were quantified.
  
  
  RESULTS
  At 1000 ppm DIM, serum IFN-γ concentrations were significantly increased (p<0.0396). The estrogen metabolites were unchanged. IFN-γ concentrations in CIN free mice and the percentage of CIN free transgenic mice were well correlated (r=0.88).
  
  
  CONCLUSIONS
  Significant increases in IFN-γ serum concentrations that correlate with the percentage of CIN free mice in each group indicate that 1000 ppm of DIM in food may be the most effective dose for future studies. These results may eventually lead to new and effective vaccination strategies in women already infected with the human papilloma virus.
authors.affiliation: The David and Alice Jurist Institute for Research, Hackensack University Medical Center, Hackensack, NJ, USA. dsepkovic@humed.com
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Sepkovic
authors.forename: Laura
authors.initials: L
authors.lastname: Raucci
authors.forename: Johann
authors.initials: J
authors.lastname: Stein
authors.forename: Antoine D
authors.initials: AD
authors.lastname: Carlisle
authors.forename: Karen
authors.initials: K
authors.lastname: Auborn
authors.forename: H Barbara
authors.initials: HB
authors.lastname: Ksieski
authors.forename: Themba
authors.initials: T
authors.lastname: Nyirenda
authors.forename: H Leon
authors.initials: HL
authors.lastname: Bradlow
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood*; D053547:Keratin-14 / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019076:Transgenes; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
chemical_list: D016588:Anticarcinogenic Agents; C068651:E6 protein, Human papillomavirus type 16; D007211:Indoles; C507540:KRT14 protein, human; D053547:Keratin-14; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D004958:Estradiol; D007371:Interferon-gamma; C001390:2-hydroxyestradiol; C016392:3,3'-diindolylmethane