A regulatory role for porphobilinogen deaminase (PBGD) in δ-aminolaevulinic acid (δ-ALA)-induced photosensitization?

被引:70
作者
Gibson, SL
Cupriks, DJ
Havens, JJ
Nguyen, ML
Hilf, R
机构
[1] Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA
[2] Univ Rochester, Sch Med & Dent, Ctr Canc, Rochester, NY 14642 USA
关键词
delta-aminolaevulinic acid; photosensitization; porphobilinogen deaminase; haem biosynthesis; porphyrin fluorescence;
D O I
10.1038/bjc.1998.39
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
As an initial approach to optimize delta-aminolaevulinic acid (delta-ALA)-induced photosensitization of tumours, we examined the response of three enzymes of the haem biosynthetic pathway: delta-ALA dehydratase, porphobilinogen deaminase (PBGD) and ferrochelatase. Only PBGD activity displayed a time-and dose-related increase in tumours after intravenous administration of 300 mo kg(-1) delta-ALA. The time course for porphyrin fluorescence changes, reflecting increased production of the penultimate porphyrin, protoporphyrin IX (PPIX), showed a similar pattern to PBGD. This apparent correlation between PBGD activity and porphyrin fluorescence was also observed in four cultured tumour cell lines exposed to 0.1-2.0 mM delta-ALA in vitro. The increase in PBGD activity and PPIX fluorescence was prevented by the protein synthesis inhibitor cycloheximide. As the apparent K-m for PBGD was similar before and after delta-ALA, the increase in PBGD activity was attributed to induction of enzyme de novo. These observations of an associated response of PBGD and PPIX imply that PBGD may be a rate-limiting determinant for the efficacy of delta-ALA-induced photosensitization when used in photodynamic therapy.
引用
收藏
页码:235 / 242
页数:8
相关论文
共 36 条
[1]   IN-VIVO KINETICS AND SPECTRA OF 5-AMINOLEVULINIC ACID-INDUCED FLUORESCENCE IN AN AMELANOTIC MELANOMA OF THE HAMSTER [J].
ABELS, C ;
HEIL, P ;
DELLIAN, M ;
KUHNLE, GEH ;
BAUMGARTNER, R ;
GOETZ, AE .
BRITISH JOURNAL OF CANCER, 1994, 70 (05) :826-833
[2]   MOLECULAR REGULATION - BIOLOGICAL ROLE OF HEME IN HEMATOPOIESIS [J].
ABRAHAM, NG .
BLOOD REVIEWS, 1991, 5 (01) :19-28
[3]   HEME PRODUCTION IN ANIMAL-TISSUES - THE REGULATION OF BIOGENESIS OF DELTA-AMINOLEVULINATE SYNTHASE [J].
ADES, IZ .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY, 1990, 22 (06) :565-578
[4]  
BAUMGARTNER R, 1993, SPIE, V1881, P20
[5]   PHOTODYNAMIC THERAPY TO SCIENTISTS AND CLINICIAN - ONE WORLD OR 2 [J].
BOWN, SG .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1990, 6 (1-2) :1-12
[6]   SUPERFICIAL PHOTODYNAMIC THERAPY WITH TOPICAL 5-AMINOLEVULINIC ACID FOR SUPERFICIAL PRIMARY AND SECONDARY SKIN-CANCER [J].
CAIRNDUFF, F ;
STRINGER, MR ;
HUDSON, EJ ;
ASH, DV ;
BROWN, SB .
BRITISH JOURNAL OF CANCER, 1994, 69 (03) :605-608
[7]   DIFFERENTIAL INTERACTION OF PORPHYRINS USED IN PHOTORADIATION THERAPY WITH FERROCHELATASE [J].
DAILEY, HA ;
SMITH, A .
BIOCHEMICAL JOURNAL, 1984, 223 (02) :441-445
[8]   LIVER FERROCHELATASE FROM NORMAL AND HEXACHLOROBENZENE PORPHYRIC RATS - STUDIES ON THEIR PROPERTIES [J].
DEMOLINA, MCR ;
TAIRA, MC ;
DEVIALE, LCSM .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY, 1989, 21 (02) :219-225
[9]  
DOUGHERTY TJ, 1978, CANCER RES, V38, P2628
[10]   CLINICAL AND PRECLINICAL PHOTODYNAMIC THERAPY [J].
FISHER, AMR ;
MURPHREE, AL ;
GOMER, CJ .
LASERS IN SURGERY AND MEDICINE, 1995, 17 (01) :2-31