Increased expression of collagen types I and III in human skin as a consequence of radiotherapy.
To study the mechanisms of irradiation-induced fibrosis, the expression of types I and III collagen was analysed in radiotherapy-treated human skin. The subjects were ten randomly chosen women who had been treated for breast cancer with surgery and radiotherapy. The subjects ranged in age from 42 to 68 years (mean 53 years) and the time from treatment ranged from 7 to 94 months. The irradiated skin was compared with a corresponding healthy skin area in the same subject. Suction blisters were induced on both skin areas. The aminoterminal propeptides of types I and III collagen (PINP and PIIINP), which reflect actual in vivo skin collagen synthesis, were determined in the suction blister fluid using radioimmunoassays. mRNA of types I and III collagen were determined in skin specimens using a nonradioactive in situ hybridization (ISH) technique. Immunohistochemical staining for PINP was also performed. The level of PINP in suction blister fluid was increased more than threefold and the level of PIIINP more than twofold in irradiated skin compared to control skin. The number of cells containing type I and type III collagen mRNA was increased in the upper dermis of irradiated skin. Immunohistochemical staining showed the amount of PINP-positive fibroblasts to be increased in irradiated skin. We conclude that skin collagen gene expression is increased as a result of irradiation and this leads to fibrosis and thickening of the dermis.
Department of Dermatology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland.
Riitta
R
Riekki
Mataleena
M
Parikka
Arja
A
Jukkola
Tuula
T
Salo
Juha
J
Risteli
Aarne
A
Oikarinen
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism*; D024061:Collagen Type III / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005355:Fibrosis; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011882:Radiotherapy, High-Energy / Q000009:adverse effects*; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*
D024042:Collagen Type I; D024061:Collagen Type III; D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide