Cargando…

Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model.

Aminolaevulinic acid (ALA) is the first committed step in haem synthesis. In the presence of excess ALA the natural regulatory feedback system is disrupted allowing accumulation of protoporphyrin IX (PP IX) the last intermediate product before haem, and an effective sensitiser. This method of endoge...

Descripción completa

Detalles Bibliográficos
Autores principales: Bedwell, J., MacRobert, A. J., Phillips, D., Bown, S. G.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1992
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977757/
https://www.ncbi.nlm.nih.gov/pubmed/1616853
_version_ 1782135330557657088
author Bedwell, J.
MacRobert, A. J.
Phillips, D.
Bown, S. G.
author_facet Bedwell, J.
MacRobert, A. J.
Phillips, D.
Bown, S. G.
author_sort Bedwell, J.
collection PubMed
description Aminolaevulinic acid (ALA) is the first committed step in haem synthesis. In the presence of excess ALA the natural regulatory feedback system is disrupted allowing accumulation of protoporphyrin IX (PP IX) the last intermediate product before haem, and an effective sensitiser. This method of endogenous photosensitisation of cells has been exploited for photodynamic therapy (PDT). We have studied the fluorescence distribution and biological effect of induced PP IX in normal and tumour tissue in the rat colon. Fluorescence in normal colonic tissue was at a peak of 4 h with a rapid fall off by 6 h. The fluorescence had returned to background levels by 24 h. All normal tissue layers followed the same fluorescence profile but the mucosa showed fluorescent levels six times higher than the submucosa, with muscle barely above background values. At 6 h the ratio of fluorescence levels between normal mucosa and viable tumour was approximately 1:6. At this time laser treatment showed necrosis of normal mucosa and tumour with sparing of normal muscle. There was good correlation between the fluorescence distribution and the biological effect of ALA-induced photosensitisation on exposure to red light. ALA may be superior to conventional sensitisers for tumours that produce haem as the PP IX is synthesised in malignant cells while the other sensitisers mainly localise to the vascular stroma of tumours. There is also a greater concentration difference between the PP IX levels in tumours and in normal mucosa and normal muscle than with the other photosensitisers raising the possibility of more selective necrosis in tumours. IMAGES:
format Text
id pubmed-1977757
institution National Center for Biotechnology Information
language English
publishDate 1992
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-19777572009-09-10 Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model. Bedwell, J. MacRobert, A. J. Phillips, D. Bown, S. G. Br J Cancer Research Article Aminolaevulinic acid (ALA) is the first committed step in haem synthesis. In the presence of excess ALA the natural regulatory feedback system is disrupted allowing accumulation of protoporphyrin IX (PP IX) the last intermediate product before haem, and an effective sensitiser. This method of endogenous photosensitisation of cells has been exploited for photodynamic therapy (PDT). We have studied the fluorescence distribution and biological effect of induced PP IX in normal and tumour tissue in the rat colon. Fluorescence in normal colonic tissue was at a peak of 4 h with a rapid fall off by 6 h. The fluorescence had returned to background levels by 24 h. All normal tissue layers followed the same fluorescence profile but the mucosa showed fluorescent levels six times higher than the submucosa, with muscle barely above background values. At 6 h the ratio of fluorescence levels between normal mucosa and viable tumour was approximately 1:6. At this time laser treatment showed necrosis of normal mucosa and tumour with sparing of normal muscle. There was good correlation between the fluorescence distribution and the biological effect of ALA-induced photosensitisation on exposure to red light. ALA may be superior to conventional sensitisers for tumours that produce haem as the PP IX is synthesised in malignant cells while the other sensitisers mainly localise to the vascular stroma of tumours. There is also a greater concentration difference between the PP IX levels in tumours and in normal mucosa and normal muscle than with the other photosensitisers raising the possibility of more selective necrosis in tumours. IMAGES: Nature Publishing Group 1992-06 /pmc/articles/PMC1977757/ /pubmed/1616853 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
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.
title Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model.
title_full Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model.
title_fullStr Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model.
title_full_unstemmed Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model.
title_short Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model.
title_sort fluorescence distribution and photodynamic effect of ala-induced pp ix in the dmh rat colonic tumour model.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977757/
https://www.ncbi.nlm.nih.gov/pubmed/1616853
work_keys_str_mv AT bedwellj fluorescencedistributionandphotodynamiceffectofalainducedppixinthedmhratcolonictumourmodel
AT macrobertaj fluorescencedistributionandphotodynamiceffectofalainducedppixinthedmhratcolonictumourmodel
AT phillipsd fluorescencedistributionandphotodynamiceffectofalainducedppixinthedmhratcolonictumourmodel
AT bownsg fluorescencedistributionandphotodynamiceffectofalainducedppixinthedmhratcolonictumourmodel