The arresting phase determines the total healing time of a locally irradiated skin wound in swine.
OBJECTIVE
Radiation is an important cause of delayed wound healing, and there still exist many questions regarding the patterns and mechanisms of wound healing. This study investigated the characteristics of wound healing after varying doses of local radiation and explored possible causes of the delay in healing caused by radiation.


METHODS
A full-thickness dorsal longitudinal skin tissue, 2 cm in diameter, was excised after local irradiation on one side of the back of swine, and the other side was wounded as a control. The size of the wound area was recorded every two days after injury. Pathological changes, proliferating cell nuclear antigen (PCNA, immunohisto- chemistry) and apoptosis levels (TUNEL assay) were measured at different time points after wounding.


RESULTS
The course of wound healing can be divided into four phases, namely: the arresting phase, the healing priming phase, the fast healing phase, and the healed phase. Although the total wound healing time was closely correlated to the dose of irradiation (R(2) equal to 0.9758), it was more dependent on the length of the arresting phase (R(2) equal to 0.9903) because once the arresting phase ended, the wound healed at a similar speed regardless of  radiation doses. Pathological analysis showed that compared with the control side there were more necrotic tissues, slower epithelial crawling, as well as fewer blood vessels and cellular components in the irradiated side at the arresting phase, while other phases revealed no significant difference concerning these measurements. Immunohistochemistry showed that the irradiated wounds had significantly less PCNA-positive and more TUNEL-positive labeling of cells in the arresting phase than in other phases. Moreover, the changes were positively related to the radiation doses, but there was no obvious difference in cell proliferation or apoptosis among the healing priming phase, fast healing phase or healed phase, whether on the control side or on  the irradiated side.


CONCLUSIONS
After local irradiation, the length of the arresting phase determines the wound healing time. Increased apoptosis and decreased cell proliferation might be an important reason for the formation of the arresting phase.
Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Ping
P
Li
En
E
Zhang
Xia
X
Liu
Jian-Zhong
JZ
Liu
Ping
P
Liu
Yan
Y
Peng
Ren-Ping
RP
Xiong
Xing-Yu
XY
Chen
Yan
Y
Zhao
Yuan-Guo
YG
Zhou
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D012867:Skin; D017695:Soft Tissue Injuries; D013552:Swine; D014945:Wound Healing