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British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Jul 24;83(4):539–543. doi: 10.1054/bjoc.2000.1300

Porphyrin biosynthesis in human Barrett's oesophagus and adenocarcinoma after ingestion of 5-aminolaevulinic acid

P Hinnen 1, F W M de Rooij 1, E M Terlouw 1, A Edixhoven 1, H van Dekken 2, R van Hillegersberg 3, H W Tilanus 3, J H P Wilson 1, P D Siersema 1
PMCID: PMC2374652  PMID: 10945504

Abstract

5-Aminolaevulinic acid (ALA)-induced porphyrin biosynthesis, which is used for ALA-based photodynamic therapy (ALA-PDT), was studied in tissues of 10 patients with Barrett’s oesophagus (BE) and adenocarcinoma of the oesophagus (AC) undergoing oesophagectomy at a mean time interval of 6.7 h after the ingestion of ALA (60 mg kg–1). In BE, AC, squamous epithelium (SQ) and gastric cardia, the activities of the haem biosynthetic enzymes porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) and the PDT power index – the ratio between PBG-D and FC in BE and AC in comparison with SQ – were determined before ALA ingestion. Following ALA administration, ALA, porphobilinogen, uroporphyrin I and PPIX were determined in tissues and plasma. The PDT power index did not predict the level of intracellular accumulation of PPIX found at 6.7 h. In BE, there was no selectivity of PPIX accumulation compared to SQ, whereas in half of patients with AC selectivity was found. Higher haem biosynthetic enzyme activities (i.e. PBG-D) and lower PPIX precursor concentrations were found in BE and AC compared to SQ. It is therefore possible that PPIX levels will peak at earlier time intervals in BE and AC compared to SQ. © 2000 Cancer Research Campaign

Keywords: photodynamic therapy, 5-aminolaevulinic acid, Barrett’s oesophagus, porphyrin biosynthesis

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Selected References

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  1. Barr H., Shepherd N. A., Dix A., Roberts D. J., Tan W. C., Krasner N. Eradication of high-grade dysplasia in columnar-lined (Barrett's) oesophagus by photodynamic therapy with endogenously generated protoporphyrin IX. Lancet. 1996 Aug 31;348(9027):584–585. doi: 10.1016/s0140-6736(96)03054-1. [DOI] [PubMed] [Google Scholar]
  2. Bishop D. F., Desnick R. J. Assays of the heme biosynthetic enzymes. Preface. Enzyme. 1982;28(2-3):91–93. [PubMed] [Google Scholar]
  3. Cameron A. J., Carpenter H. A. Barrett's esophagus, high-grade dysplasia, and early adenocarcinoma: a pathological study. Am J Gastroenterol. 1997 Apr;92(4):586–591. [PubMed] [Google Scholar]
  4. Clark G. W., Ireland A. P., DeMeester T. R. Dysplasia in Barrett's esophagus: diagnosis, surveillance and treatment. Dig Dis. 1996 Jul-Aug;14(4):213–227. doi: 10.1159/000171554. [DOI] [PubMed] [Google Scholar]
  5. Drewitz D. J., Sampliner R. E., Garewal H. S. The incidence of adenocarcinoma in Barrett's esophagus: a prospective study of 170 patients followed 4.8 years. Am J Gastroenterol. 1997 Feb;92(2):212–215. [PubMed] [Google Scholar]
  6. Edwards M. J., Gable D. R., Lentsch A. B., Richardson J. D. The rationale for esophagectomy as the optimal therapy for Barrett's esophagus with high-grade dysplasia. Ann Surg. 1996 May;223(5):585–591. doi: 10.1097/00000658-199605000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goldberg A., McGillion F. B. Proceedings: Central uptake and cardiovascular effects of delta-aminolaevulinic acid. Br J Pharmacol. 1973 Sep;49(1):178P–178P. [PMC free article] [PubMed] [Google Scholar]
  8. Gossner L., Stolte M., Sroka R., Rick K., May A., Hahn E. G., Ell C. Photodynamic ablation of high-grade dysplasia and early cancer in Barrett's esophagus by means of 5-aminolevulinic acid. Gastroenterology. 1998 Mar;114(3):448–455. doi: 10.1016/s0016-5085(98)70527-x. [DOI] [PubMed] [Google Scholar]
  9. Haggitt R. C. Barrett's esophagus, dysplasia, and adenocarcinoma. Hum Pathol. 1994 Oct;25(10):982–993. doi: 10.1016/0046-8177(94)90057-4. [DOI] [PubMed] [Google Scholar]
  10. Hameeteman W., Tytgat G. N., Houthoff H. J., van den Tweel J. G. Barrett's esophagus: development of dysplasia and adenocarcinoma. Gastroenterology. 1989 May;96(5 Pt 1):1249–1256. doi: 10.1016/s0016-5085(89)80011-3. [DOI] [PubMed] [Google Scholar]
  11. Henderson B. W., Dougherty T. J. How does photodynamic therapy work? Photochem Photobiol. 1992 Jan;55(1):145–157. doi: 10.1111/j.1751-1097.1992.tb04222.x. [DOI] [PubMed] [Google Scholar]
  12. Herman M. A., Webber J., Fromm D., Kessel D. Hemodynamic effects of 5-aminolevulinic acid in humans. J Photochem Photobiol B. 1998 Apr;43(1):61–65. doi: 10.1016/S1011-1344(98)00086-4. [DOI] [PubMed] [Google Scholar]
  13. Hinnen P., De Rooij F. W., Voortman G., Tilanus H. W., Wilson J. H., Siersema P. D. Acrylate yellow filters in operating lights protect against photosensitization tissue damage. Br J Surg. 2000 Feb;87(2):231–235. doi: 10.1046/j.1365-2168.2000.01325.x. [DOI] [PubMed] [Google Scholar]
  14. Hinnen P., de Rooij F. W., van Velthuysen M. L., Edixhoven A., van Hillegersberg R., Tilanus H. W., Wilson J. H., Siersema P. D. Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus. Br J Cancer. 1998 Sep;78(5):679–682. doi: 10.1038/bjc.1998.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Kennedy J. C., Pottier R. H. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B. 1992 Jul 30;14(4):275–292. doi: 10.1016/1011-1344(92)85108-7. [DOI] [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Li G., Szewczuk M. R., Pottier R. H., Kennedy J. C. Effect of mammalian cell differentiation on response to exogenous 5-aminolevulinic acid. Photochem Photobiol. 1999 Feb;69(2):231–235. [PubMed] [Google Scholar]
  19. Regula J., MacRobert A. J., Gorchein A., Buonaccorsi G. A., Thorpe S. M., Spencer G. M., Hatfield A. R., Bown S. G. Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX--a pilot study. Gut. 1995 Jan;36(1):67–75. doi: 10.1136/gut.36.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. van den Boogert J., van Hillegersberg R., de Rooij F. W., de Bruin R. W., Edixhoven-Bosdijk A., Houtsmuller A. B., Siersema P. D., Wilson J. H., Tilanus H. W. 5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration. J Photochem Photobiol B. 1998 Jun 15;44(1):29–38. doi: 10.1016/s1011-1344(98)00102-x. [DOI] [PubMed] [Google Scholar]
  22. van der Burgh A., Dees J., Hop W. C., van Blankenstein M. Oesophageal cancer is an uncommon cause of death in patients with Barrett's oesophagus. Gut. 1996 Jul;39(1):5–8. doi: 10.1136/gut.39.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]

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