Harvey-ras gene expression and epidermal cell proliferation in dibenzo[a,I]pyrene-treated early preneoplastic SENCAR mouse skin

Gausal A. Khan, Gautam Bhattacharya, Paula C. Mailander, Jane L. Meza, Laura A. Hansen, Dhrubajyoti Chakravarti

Research output: Contribution to journalArticle

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Abstract

Topical application of dibenzo[a,I]pyrene (DB[a,I]P) to the dorsal skin of SENCAR mice induces codon 61 (CAAGln to CTALeu) mutations in the Harvey (H)-ras gene within 12 h after treatment. Between days 1 and 3, the frequency of these mutations increases rapidly, suggesting that skin cells carrying the codon 61 mutations proliferate in this period. We have investigated DB[a,I]P-treated mouse skin (12 h-7 d) for further evidence of H-ras expression and epidermal cell proliferation. Two waves of cell proliferation were observed: the first wave (1-2 d) correlated with the clonal proliferation of codon 61-mutated cells, and the second wave (3-7 d) correlated with DB[a,I]P-induced hyperplasia. DB[a,I]P-induced early preneoplastic cell proliferation correlated with H-ras and specific G1 cyclin expression. Total H-ras protein and cyclin D1 were found to increase during DB[a,I]P-induced hyperplasia, but the levels of guanosine triphosphate-bound (active) H-ras protein and cyclin E were increased during the putative clonal proliferation of codon 61-mutated cells. These results suggest that DB[a,I]P-induced oncogenically mutated cells proliferate in early preneoplastic skin. As this proliferation occurs in the absence of any promoting treatment, we propose that this phenomenon is a tumor initiation event.

Original languageEnglish
Pages (from-to)567-574
Number of pages8
JournalJournal of Investigative Dermatology
Volume125
Issue number3
DOIs
StatePublished - Sep 2005

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Inbred SENCAR Mouse
ras Genes
Cell proliferation
Gene expression
Codon
Skin
Cell Proliferation
Gene Expression
ras Proteins
Hyperplasia
Cyclin G1
Cyclin E
Mutation
Cyclin D1
Mutation Rate
Guanosine Triphosphate
Tumors
Genes
pyrene
Neoplasms

All Science Journal Classification (ASJC) codes

  • Dermatology

Cite this

Harvey-ras gene expression and epidermal cell proliferation in dibenzo[a,I]pyrene-treated early preneoplastic SENCAR mouse skin. / Khan, Gausal A.; Bhattacharya, Gautam; Mailander, Paula C.; Meza, Jane L.; Hansen, Laura A.; Chakravarti, Dhrubajyoti.

In: Journal of Investigative Dermatology, Vol. 125, No. 3, 09.2005, p. 567-574.

Research output: Contribution to journalArticle

Khan, Gausal A. ; Bhattacharya, Gautam ; Mailander, Paula C. ; Meza, Jane L. ; Hansen, Laura A. ; Chakravarti, Dhrubajyoti. / Harvey-ras gene expression and epidermal cell proliferation in dibenzo[a,I]pyrene-treated early preneoplastic SENCAR mouse skin. In: Journal of Investigative Dermatology. 2005 ; Vol. 125, No. 3. pp. 567-574.
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