Abstract
Samples of human and rat skin in short-term organ culture exposed to ALA or a range of hydrophobic derivatives were examined for their effect on the accumulation of protoporphyrin IX (PpIX) measured using fluorescence spectroscopy. With the exception of carbobenzoyloxy-D-phenylalanyl-5-ALA-ethyl ester the data presented indicate that, in normal tissues, ALA derivatives generate protoporphyrin IX more slowly than ALA, suggesting that they are less rapidly taken up and/or converted to free ALA. However, the resultant depot effect may lead to the enhanced accumulation of porphyrin over long exposure periods, particularly in the case of ALA-methyl ester or ALA-hexyl ester, depending on the applied concentration and the exposed tissue. Addition of the iron chelator, CP94, greatly increased PpIX accumulation in human skin exposed to ALA, ALA-methyl ester and ALA-hexyl ester. The effect in rat skin was less marked. © 1999 Cancer Research Campaign
Keywords: ALA, PDT, ALA derivatives, ALA esters, iron chelators, CP94
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- Bech O., Phillips D., Moan J., MacRobert A. J. A hydroxypyridinone (CP94) enhances protoporphyrin IX formation in 5-aminolaevulinic acid treated cells. J Photochem Photobiol B. 1997 Nov;41(1-2):136–144. doi: 10.1016/s1011-1344(97)00095-x. [DOI] [PubMed] [Google Scholar]
- Bedwell J., MacRobert A. J., Phillips D., Bown S. G. Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model. Br J Cancer. 1992 Jun;65(6):818–824. doi: 10.1038/bjc.1992.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berg K., Anholt H., Bech O., Moan J. The influence of iron chelators on the accumulation of protoporphyrin IX in 5-aminolaevulinic acid-treated cells. Br J Cancer. 1996 Sep;74(5):688–697. doi: 10.1038/bjc.1996.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bermúdez Moretti M., Correa García S. R., Chianelli M. S., Ramos E. H., Mattoon J. R., Batlle A. Evidence that 4-aminobutyric acid and 5-aminolevulinic acid share a common transport system into Saccharomyces cerevisiae. Int J Biochem Cell Biol. 1995 Feb;27(2):169–173. doi: 10.1016/1357-2725(95)00002-7. [DOI] [PubMed] [Google Scholar]
- Chang S. C., MacRobert A. J., Porter J. B., Bown S. G. The efficacy of an iron chelator (CP94) in increasing cellular protoporphyrin IX following intravesical 5-aminolaevulinic acid administration: an in vivo study. J Photochem Photobiol B. 1997 Apr;38(2-3):114–122. doi: 10.1016/s1011-1344(96)07441-6. [DOI] [PubMed] [Google Scholar]
- Curnow A., McIlroy B. W., Postle-Hacon M. J., Porter J. B., MacRobert A. J., Bown S. G. Enhancement of 5-aminolaevulinic acid-induced photodynamic therapy in normal rat colon using hydroxypyridinone iron-chelating agents. Br J Cancer. 1998 Nov;78(10):1278–1282. doi: 10.1038/bjc.1998.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dietel W., Bolsen K., Dickson E., Fritsch C., Pottier R., Wendenburg R. Formation of water-soluble porphyrins and protoporphyrin IX in 5-aminolevulinic-acid-incubated carcinoma cells. J Photochem Photobiol B. 1996 May;33(3):225–231. doi: 10.1016/1011-1344(95)07249-7. [DOI] [PubMed] [Google Scholar]
- Fritsch C., Batz J., Bolsen K., Schulte K. W., Zumdick M., Ruzicka T., Goerz G. Ex vivo application of delta-aminolevulinic acid induces high and specific porphyrin levels in human skin tumors: possible basis for selective photodynamic therapy. Photochem Photobiol. 1997 Jul;66(1):114–118. doi: 10.1111/j.1751-1097.1997.tb03146.x. [DOI] [PubMed] [Google Scholar]
- Fukuda H., Paredes S., Batlle A. M. Tumor-localizing properties of porphyrins. In vitro studies using the porphyrin precursor, aminolevulinic acid, in free and liposome encapsulated forms. Drug Des Deliv. 1989 Dec;5(2):133–139. [PubMed] [Google Scholar]
- Fukuda H., Paredes S., Batlle A. M. Tumour-localizing properties of porphyrins. In vivo studies using free and liposome encapsulated aminolevulinic acid. Comp Biochem Physiol B. 1992 Jun;102(2):433–436. doi: 10.1016/0305-0491(92)90147-j. [DOI] [PubMed] [Google Scholar]
- García S. C., Moretti M. B., Garay M. V., Batlle A. Delta-aminolevulinic acid transport through blood-brain barrier. Gen Pharmacol. 1998 Oct;31(4):579–582. doi: 10.1016/s0306-3623(98)00038-x. [DOI] [PubMed] [Google Scholar]
- Gaullier J. M., Berg K., Peng Q., Anholt H., Selbo P. K., Ma L. W., Moan J. Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cancer Res. 1997 Apr 15;57(8):1481–1486. [PubMed] [Google Scholar]
- Hanania J., Malik Z. The effect of EDTA and serum on endogenous porphyrin accumulation and photodynamic sensitization of human K562 leukemic cells. Cancer Lett. 1992 Aug 14;65(2):127–131. doi: 10.1016/0304-3835(92)90156-p. [DOI] [PubMed] [Google Scholar]
- Iinuma S., Farshi S. S., Ortel B., Hasan T. A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin. Br J Cancer. 1994 Jul;70(1):21–28. doi: 10.1038/bjc.1994.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kloek J., Akkermans W., Beijersbergen van Henegouwen G. M. Derivatives of 5-aminolevulinic acid for photodynamic therapy: enzymatic conversion into protoporphyrin. Photochem Photobiol. 1998 Jan;67(1):150–154. [PubMed] [Google Scholar]
- Kloek J., Beijersbergen van Henegouwen Prodrugs of 5-aminolevulinic acid for photodynamic therapy. Photochem Photobiol. 1996 Dec;64(6):994–1000. doi: 10.1111/j.1751-1097.1996.tb01868.x. [DOI] [PubMed] [Google Scholar]
- Navone N. M., Polo C. F., Frisardi A. L., Andrade N. E., Battle A. M. Heme biosynthesis in human breast cancer--mimetic "in vitro" studies and some heme enzymic activity levels. Int J Biochem. 1990;22(12):1407–1411. doi: 10.1016/0020-711x(90)90230-z. [DOI] [PubMed] [Google Scholar]
- Ortel B., Tanew A., Hönigsmann H. Lethal photosensitization by endogenous porphyrins of PAM cells--modification by desferrioxamine. J Photochem Photobiol B. 1993 Mar;17(3):273–278. doi: 10.1016/1011-1344(93)80025-5. [DOI] [PubMed] [Google Scholar]
- Peng Q., Moan J., Warloe T., Iani V., Steen H. B., Bjørseth A., Nesland J. M. Build-up of esterified aminolevulinic-acid-derivative-induced porphyrin fluorescence in normal mouse skin. J Photochem Photobiol B. 1996 Jun;34(1):95–96. doi: 10.1016/1011-1344(95)07268-3. [DOI] [PubMed] [Google Scholar]
- Peng Q., Warloe T., Berg K., Moan J., Kongshaug M., Giercksky K. E., Nesland J. M. 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges. Cancer. 1997 Jun 15;79(12):2282–2308. doi: 10.1002/(sici)1097-0142(19970615)79:12<2282::aid-cncr2>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
- Rebeiz N., Rebeiz C. C., Arkins S., Kelley K. W., Rebeiz C. A. Photodestruction of tumor cells by induction of endogenous accumulation of protoporphyrin IX: enhancement by 1,10-phenanthroline. Photochem Photobiol. 1992 Mar;55(3):431–435. doi: 10.1111/j.1751-1097.1992.tb04258.x. [DOI] [PubMed] [Google Scholar]
- Van Hillegersberg R., Van den Berg J. W., Kort W. J., Terpstra O. T., Wilson J. H. Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats. Gastroenterology. 1992 Aug;103(2):647–651. doi: 10.1016/0016-5085(92)90860-2. [DOI] [PubMed] [Google Scholar]
- Washbrook R., Fukuda H., Battle A., Riley P. Stimulation of tetrapyrrole synthesis in mammalian epithelial cells in culture by exposure to aminolaevulinic acid. Br J Cancer. 1997;75(3):381–387. doi: 10.1038/bjc.1997.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Washbrook R., Riley P. A. Comparison of delta-aminolaevulinic acid and its methyl ester as an inducer of porphyrin synthesis in cultured cells. Br J Cancer. 1997;75(10):1417–1420. doi: 10.1038/bjc.1997.244. [DOI] [PMC free article] [PubMed] [Google Scholar]