Reference SummaryBinder RL, Cancer Res 1998 Oct 1;58(19):4314-23

Title

 Squamous cell hyperplastic foci: precursors of cutaneous papillomas induced in SENCAR mice by a two-stage carcinogenesis regimen.

Authors

 Binder RL; Johnson GR; Gallagher PM; Stockman SL; Sundberg JP; Conti CJ

Journal

 Cancer Res

Volume

 58

Issue

 19

Year

 1998

Pages

 4314-23

Abstract

 We have conducted a series of experiments to characterize the lesions that are precursors of cutaneous papillomas in SENCAR mice initiated with 7,12-dimethylbenz(a)anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). The first grossly detectable lesions at sites where papillomas subsequently developed were papules, slightly raised areas of skin ranging in diameter from 0.25 to approximately 1.5 mm. Papules were first detected in DMBA-initiated mice 21 days after the start of dosing with TPA. Of 78 DMBA/TPA-induced papules tracked during 15 weeks of TPA treatments, 68% progressed to papillomas, 9% persisted as papules, and 22% completely regressed. Histological evaluation of serial sections of 69 DMBA/TPA-induced papules revealed that they were focal hyperplastic lesions that we refer to as squamous cell hyperplastic foci (SCHF). These hyperproliferative lesions appeared to progress through two distinct stages. Stage I SCHF were characterized as regular hyperplastic foci involving the interfollicular epidermis and the outer root sheaths of 1 or more hair follicles down to the level of the sebaceous glands. Stage II SCHF were foci of irregular epithelial hyperplasia with increased fibrovascular stroma and involved from 3 to >10 hair follicles. Prominent dilated capillaries and inflammatory cell infiltrates were frequently associated with both stage I and II SCHF. Ha-ras gene codon 61 mutations were detected in 7 of 10 stage I SCHF and 13 of 14 stage II SCHF microdissected from histological sections and 7 of 7 of whole papules by mutation-specific PCR analysis. These data provide molecular evidence that SCHF are foci of initiated cells. Further study of these lesions may contribute to more fully defining the sequence of molecular and cellular changes necessary for tumorigenesis in mouse skin. SCHF may also have utility as early indicators of potential skin tumorigenicity in cancer bioassays.

Links

 J:50210 – MGI References
9766659 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
SENCAR Skin - Epidermis hyperplasia
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Skin - Epidermis

75
SENCAR Skin hyperplasia Skin

0
SENCAR Skin hyperplasia
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
 Skin

0
SENCAR Skin papilloma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
 Skin

0
SENCAR Skin papilloma
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Skin

0
SENCAR Skin squamous cell hyperplasia
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Skin

0 - 100
SENCAR Skin squamous cell hyperplasia
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Skin

0 - observed
SENCAR Skin squamous cell papilloma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Skin

very high