Increased skin carcinogenesis in caspase-activated DNase knockout mice.
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.
Yan
Bin
B
Department of Radiation Oncology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA.
Wang
Huili
H
Xie
Donghua
D
Wakamatsu
Nobuko
N
Anscher
Mitchell S
MS
Dewhirst
Mark W
MW
Mitchel
Ron E J
RE
Chen
Benny J
BJ
Li
Chuan-Yuan
CY
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017124:Conserved Sequence; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D053938:DNA Fragmentation; D017931:DNA Primers; D003851:Deoxyribonucleases / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009367:Neoplasm Staging; D009707:Nucleosomes / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D009707:Nucleosomes; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease