BACTERIOCHLOROPHYLL-A AS PHOTOSENSITIZER FOR PHOTODYNAMIC TREATMENT OF TRANSPLANTABLE MURINE TUMORS

被引:62
作者
HENDERSON, BW
SUMLIN, AB
OWCZARCZAK, BL
DOUGHERTY, TJ
机构
[1] Division of Radiation Biology, Roswell Park Cancer Institute, Buffalo, NY
关键词
PHOTODYNAMIC THERAPY; BACTERIOCHLOROPHYLL-A; BACTERIOPHEOPHYTIN-A; TRANSPLANTABLE MOUSE TUMOR PHOTOSENSITIZATION;
D O I
10.1016/1011-1344(91)80016-B
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bacteriochlorophyll-a (bChla), which absorbs light of 780 nm wavelength, was tested for in vivo photodynamic activity in the SMT-F and RIF transplantable mouse tumor systems. High performance liquid chromatography (HPLC) analysis of tissue extracts showed that bChla was rapidly degraded in vivo to bacteriopheophytin-a (bPheoa) and other breakdown products. These were also photodynamically active, and tumor response could be achieved over a wavelength range of 660 to 780 nm, while tumor cure was restricted to wavelengths of 755 (bPheoa) to 780 nm. A photosensitizing product absorbing at 660 nm was also present in isolated tumor cells. Photodynamic cell kill of tumor cells isolated from tumors after bChla accumulation in vivo, using 755 or 780 nm light in vitro, was exponential up to 20-40 J cm-2. Above this light dose little or no further damage could be achieved, which is an indication of the rapid photobleaching of these sensitizers. In vivo, vascular occlusion occurred readily if light treatment was delivered shortly after sensitizer administration, but was delayed if light treatment was carried out 24 h after injection. Although up to 70% of tumor cells were lethally damaged after completion of in vivo light treatment, concurrent severe vascular destruction seemed necessary for tumor cure. Normal tissue photosensitivity totally subsided within 5 days after sensitizer administration.
引用
收藏
页码:303 / 313
页数:11
相关论文
共 11 条
[1]   PHOTOPHYSICAL STUDIES OF BACTERIOCHLOROPHYLL-A AND BACTERIOPHEOPHYTIN-A - SINGLET OXYGEN GENERATION [J].
BORLAND, CF ;
MCGARVEY, DJ ;
TRUSCOTT, TG ;
CODGELL, RJ ;
LAND, EJ .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1987, 1 (01) :93-101
[2]   PHOTORADIATION THERAPY .2. CURE OF ANIMAL TUMORS WITH HEMATOPORPHYRIN AND LIGHT [J].
DOUGHERTY, TJ ;
GRINDEY, GB ;
FIEL, R ;
WEISHAUPT, KR ;
BOYLE, DG .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1975, 55 (01) :115-121
[3]   PHOTODYNAMIC THERAPY - NEW APPROACHES [J].
DOUGHERTY, TJ .
SEMINARS IN SURGICAL ONCOLOGY, 1989, 5 (01) :6-16
[4]   DRUG AND LIGHT DOSE DEPENDENCE OF PHOTODYNAMIC THERAPY - A STUDY OF TUMOR AND NORMAL TISSUE-RESPONSE [J].
FINGAR, VH ;
HENDERSON, BW .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1987, 46 (05) :837-841
[5]  
GOMER CJ, 1990, FUTURE DIRECTIONS AP, P139
[6]  
HENDERSON BW, 1985, CANCER RES, V45, P572
[7]  
HENDERSON BW, 1990, FUTURE DIRECTIONS AP, P153
[8]  
KRASNOVSKII AA, 1985, DOKL AKAD NAUK SSSR+, V283, P474
[9]   PHOTO-LUMINESCENCE OF SINGLET OXYGEN IN PIGMENT SOLUTIONS [J].
KRASNOVSKY, AA .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1979, 29 (01) :29-36
[10]  
Krasnovsky Jr A.A., 1982, BIOPHYSICS-USSR, V27, P1009