title: Oral chemoprevention of skin cancer in mice by benzophenone sunscreens dioxybenzone and octabenzone in drinking water.
abstract: BACKGROUND
  Sunscreen compounds with added benefit of skin cancer prevention have both public and commercial interests. Our earlier study using the Epstein-Barr virus early antigen in vitro assay reported on skin cancer chemoprevention potential of benzophenone sunscreens. We now report the in vivo antitumor activity of two of the benzophenone sunscreens which tested positively in the in vitro assay, octabenzone (UV-1) and dioxybenzone (UV-2), in the two-stage mouse skin carcinogenesis model using (±)-(E)-4-methyl-2-[-(E)-hydroxyamino]-5-nitro-6-methoxy-3-hexanamide (NOR-1) as inducer and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) as promoter.
  
  
  METHODS
  Pathogen-free, female hairless mice of HOS:HR-1 strain, 15 animals per control and test groups, were used. Skin tumors were induced by a single dose of NOR-1 (390 nmol in 100 μl of acetone). One week later, TPA (1.7 nmol in 100 μl of acetone) was applied to skin twice weekly for 20 weeks as tumor a promoter. The test compounds UV-I or UV-2 were administered at 0.0025% to mice through drinking water ad libitum, starting one week prior to and stopping one week after tumor initiation. All animals were examined weekly for the development of skin papillomas.
  
  
  RESULTS
  In both UV-1- and UV-2-treated mice, a two-week delay in tumor appearance, and significant inhibition (p<0.001) of tumor incidence (50% and 60%, respectively) and tumor burden (papilloma inhibition/mouse, 50% and 70%, respectively) were observed when compared to the positive control group. UV-2 (dihydroxy derivative) was a more potent inhibitor of skin tumor than UV-1 (monohydroxy derivative), which followed their antioxidant activity ranking.
  
  
  CONCLUSIONS
  The results affirm the skin cancer chemoprevention potential of orally-ingested benzophenone sunscreens in mice and warrant studies in humans to validate synergistic protection achievable by complementation of oral and topical sunscreen usage.
authors.affiliation: Global Technology Resource Center, Streamwood, IL, USA.
authors.forename: G Subba
authors.initials: GS
authors.lastname: Rao
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Ichiishi
authors.forename: Midori
authors.initials: M
authors.lastname: Takasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Iida
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Suzuki
authors.forename: Takao
authors.initials: T
authors.lastname: Konoshima
authors.forename: Govind J
authors.initials: GJ
authors.lastname: Kapadia
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001577:Benzophenones / Q000008:administration & dosage* / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic; D060766:Drinking Water; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D013473:Sunscreening Agents / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D016588:Anticarcinogenic Agents; D001577:Benzophenones; D060766:Drinking Water; D013473:Sunscreening Agents; C047723:benzophenone; C004839:dioxybenzone
keywords: Benzophenone sunscreens; antioxidants; dioxybenzone; mouse skin papillomas; octabenzone; oral chemoprevention