Increased skin carcinogenesis in caspase-activated DNase knockout mice.

Journal Article

Caspase-activated DNase (CAD), also called DNA fragmentation factor (DFF), is the enzyme responsible for DNA fragmentation during apoptosis, a hallmark of programmed cell death. CAD/DFF has been shown to suppress radiation-induced carcinogenesis by preventing genomic instability in cells. In this study, we have investigated the role of CAD in chemical carcinogenesis using CAD-null mice and two-stage model of skin carcinogenesis. After topical treatment of mouse skin with dimethylbenz[a]anthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoting agent, there was a 4-fold increase in the number of papillomas per mouse and 50.8% increase in the incidence of papilloma formation in the CAD knockout mice compared with wild-type littermates. The papillomas in CAD-null mice grew faster and reached larger sizes. These data indicate that loss of CAD function enhances tumorigenesis induced by a chemical carcinogen in the DMBA/TPA two-stage model of skin carcinogenesis in mice.

Full Text

Duke Authors

Cited Authors

  • Yan, B; Wang, H; Xie, D; Wakamatsu, N; Anscher, MS; Dewhirst, MW; Mitchel, REJ; Chen, BJ; Li, C-Y

Published Date

  • October 2009

Published In

Volume / Issue

  • 30 / 10

Start / End Page

  • 1776 - 1780

PubMed ID

  • 19541853

Electronic International Standard Serial Number (EISSN)

  • 1460-2180

Digital Object Identifier (DOI)

  • 10.1093/carcin/bgp146

Language

  • eng

Conference Location

  • England