Protective effect of prostaglandin E₁ on radiation-induced proliferative inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in rats.
We examined the effects of prostaglandin E₁ (PGE₁) on radiation-induced proliferation inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in a rat model. PGE₁ had a protective effect on radiation-induced growth inhibition in keratinocytes in vitro, but not in fibroblasts. Varying concentrations of PGE₁ were subcutaneously administered into the posterior neck region. X-irradiation at a dose of 20 Gy was administrated to the lower part of the back using a lead sheet with two holes 30 min to 1 h before or after the administration of PGE₁. Although X-irradiation induced epilation, minor erosions, or skin ulcers in almost all rats, PGE₁ administration prior to irradiation reduced these irradiation injuries. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling showed that proportions of apoptotic keratinocytes in the X-irradiated skin of PGE₁-administered rats were significantly lower than for those in the skin of rats which did not receive PGE₁. Cutaneous full-thickness defective wounds were then formed in X-irradiated areas to examine the time course of wound healing. Wound healing was significantly delayed because of X-irradiation, but PGE₁ administration prior to irradiation led to a significantly shorter delay in wound healing compared with controls. Decreasing delay in wound healing was correlated with concentration of PGE₁ administrated. Thus, PGE₁-administration may potentially alleviate the radiation-induced skin injury.
Department of Plastic Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
Megumi
M
Takikawa
Yuki
Y
Sumi
Yoshihiro
Y
Tanaka
Masaki
M
Nambu
Takashi
T
Doumoto
Satoshi
S
Yanagibayashi
Ryuichi
R
Azuma
Naoto
N
Yamamoto
Satoko
S
Kishimoto
Masayuki
M
Ishihara
Tomoharu
T
Kiyosawa
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008297:Male; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011855:Radiodermatitis / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000293:injuries* / Q000473:pathology / Q000528:radiation effects*; D014945:Wound Healing / Q000187:drug effects
D011837:Radiation-Protective Agents; D000527:Alprostadil