UVA1 irradiation induces deoxyribonuclease dependent apoptosis in cutaneous T-cell lymphoma in vivo.
Cutaneous T-cell lymphoma (CTCL) is a malignancy of mature T-cells, predominantly of the helper phenotype, that primarily invade the skin. Different photo- and chemotherapeutic treatments are known to be beneficial in early-stage CTCL. This observation has initiated prospective investigations into the efficacy of phototherapeutic regimens. The purpose of our study was to investigate the ability of medium-dose UVA1 phototherapy (60 J/cm2) to induce apoptosis (programmed cell death) in skin infiltrating T-cells of CTCL in vivo. We describe the results of three different staining methods for formalin-fixed, paraffin-embedded tissue sections. The in situ end-labeling (ISEL) procedure, nuclear staining using the DNA-binding fluorochrome Hoechst 33342, and immunohistochemistry using polyclonal antibodies against recombinant mouse deoxyribonuclease I (DNase I) demonstrated that UVA1 irradiation was able to induce marked apoptosis in CTCL. Thereby, ISEL and Hoechst staining clearly revealed DNA-condensation and nuclear fragmentation, accompanied by the formation of typical "apoptotic bodies". The accumulation of DNase I immunoreactivity in the cytoplasm of lymphocytes in UVA1 irradiated skin indicated that DNase I or DNase I-related endonucleases may have acted as apoptotic endonuclease(s) which were synthesized after UVA1 irradiation prior to their apoptotic elimination.
von Kobyletzki
G
G
Department of Dermatology, Ruhr University, Bochum, Germany. Gregor.vonKobyletzki@ruhr-uni-bochum.de
Heine
O
O
Stephan
H
H
Pieck
C
C
Stücker
M
M
Hoffmann
K
K
Altmeyer
P
P
Mannherz
H G
HG
D000368:Aged; D017209:Apoptosis / Q000528:radiation effects*; D001562:Benzimidazoles; D002467:Cell Nucleus / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism* / Q000528:radiation effects; D005456:Fluorescent Dyes; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D011879:Radiotherapy Dosage; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D014467:Ultraviolet Therapy
D001562:Benzimidazoles; D005456:Fluorescent Dyes; D003850:Deoxyribonuclease I; C017807:bisbenzimide ethoxide trihydrochloride