Mechanisms of Toxicity of Photoactivated Artificial Porphyrins Role of Porphyrin‐Protein Interactions

Smith, Ann

doi:10.1111/j.1749-6632.1987.tb48786.x

Cited by 21 publications

(21 citation statements)

References 48 publications

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“…Co-administration of 5 ;g ml-' desferal and ALA significantly increased PpIX accumulation in all carcinoma cell lines but not in normal cell lines. Several reports showed that ferrochelatase activity of hepatoma tissue was lower than that of normal liver tissue (Smith, 1987;Hillegersberg et al, 1992). It is likely that 5 lg ml1' desferal was enough to increase PpIX accumulation in malignant cell lines via decreasing ferrochelatase activity to a negligible level.…”

Section: Discussionmentioning

confidence: 99%

A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin

Iinuma

Farshi²,

Ortel³

et al. 1994

Br J Cancer

237

122

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Section: Discussionmentioning

confidence: 99%

A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin

Iinuma

Farshi²,

Ortel³

et al. 1994

Br J Cancer

237

122

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“…Dailey and Smith (1984) found a decreased FC activity in the Morris hepatoma model; however, they also pointed out that some porphyrins can act as inhibitors of FC. Smith (1987) found decreased FC activities in human skin tumours but also in normal skin tissue compared with those in rat liver mitochondria. El-Sharabasy et al (1992) determined the FC activity in whole-blood samples of children and adults with acute lymphoblastic leukaemia (ALL).…”

mentioning

confidence: 79%

Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus

Hinnen

Rooij²,

Velthuysen³

et al. 1998

Br J Cancer

118

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Summary Administration of 5-aminolaevulinic acid (ALA) leads to porphyrin accumulation in malignant and premalignant tissues, and ALA is used as a prodrug in photodynamic therapy (PDT). To understand the mechanism of porphyrin accumulation after the administration of ALA and to investigate whether ALA-induced protoporphyrin IX Correspondence to: FWM de Rooij lead to the development of adenocarcinoma through a multistep process of progression from metaplasia to lo%--agrade dysplasia.high-grade dysplasia and ultimately to invasixe cancer (Hamilton and Smith. 1987: Hameeteman et al. 1989). High-grade dysplasia in Barrett's oesophagus presents a difficult management problem.Options include endoscopic sun eillance and/or oesophagectomr (Lexine et al. 1993: Clark et al. 1996: Cameron. 1997. A new nonsurgical management option involhes eradicating the dysplastic epithelium and columnar mucosa by PDT. In contrast to other photosensitizers. mans of which localize in the microxvasculature of all tissue layers of hollow organs. ALA induces much higher levels of PPIX in the mucosa than submucosa or muscularis mucosae (Loh et al. 1993). ALA-PDT has been used to treat high-grade dy splasia in Barrett's oesophagus. resulting in necrosis of dysplastic mucosa with regeneration of normal squamous mucosa (Gossner et al. 1995: Reaula et al. 1995: Barr et al. 1996.To optimize ALA-PDT for Barrett's oesophagus and early carcinoma. knowledae of the mechanism of porphyrin accumulation in these tissues is required. We determined the activities of PBG-D and FC in normal tissue as well as in malignant and premalignant tissue of the human oesophagrus. These tw o enzymes play an important role after the administration of ALA: PBG-D is in many cells the rate-limiting enzyme w-hen exogenous ALA is administered and FC is the enzN-me directly responsible for the conx ersion of PPIX to haem. We propose the use of a PDT power index for the intertissue variation in the abilitv to accumulate PPIX. in order to create a parameter that might indicate the susceptibilitv of tissues to ALA-PDT. 679

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“…The reason for low ferrochelatase activity in tumours may be the use of glycolysis rather than oxidative phosphorylation for their metabolism. In particular, rapdily growing tumours contain lower activities of mitochondrial cytochrome oxidase (Smith, 1987). Mitochondrial ferrfchelatase would therefore be deficient secondary to deficiencies in mitochondrial cytochrome oxidase (Rimington and Riley, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…The reason for selective porphyrin accumulation in malignant tissue after ALA may be an altered activity of the haem biosynthetic pathway enzymes. Several studies have reported a higher activity of porphobilinogen deaminase (PBGD) in malignant and regenerating cells, whereas the opposite was found for ferrochelatase (Smith, 1987;Schoenfeld et al, 1988). PBGD catalyses the formation of uroporphyrinogen (URO) from four molecules of porphobilinogen and ferrochelatase converts protoporphyrin to haem.…”

mentioning

confidence: 99%

Adjuvant intraoperative photodynamic therapy diminishes the rate of local recurrence in a rat mammary tumour model

Hillegersberg

Hekking‐Weijma²,

Wilson³

et al. 1995

Br J Cancer

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Summary The use of photodynamic therapy (PDT) as an adjunct to curative tumour resection was investigated in a tumour recurrence model, using rat mammary adenocarcinoma BN472. Tumours were inoculated subcutaneously in 60 animals and resected after 21 days of growth. Immediately after removal, the operation site was exposed to 320-450 nm light of 0.1 W cm2 and 60 J cm-2 after photosensitisation with either Photofrin (5 mg kg-' i.v. 48 h before illumination) or 5-aminolaevulinic acid (ALA) (2mg ml-' in drinking water for 9 days). Porphyrin concentrations were measured in tissue samples. After 28 days, animals treated with adjunctive PDT had a significantly longer tumour-free interval than controls (P<0.01); median 25 days (Photofrin), 18 days (ALA), 14 days (controls). Moreover, in the PDT groups significantly fewer rats had lymph node metastasis. A porphyrin concentration ratio between tumour and mammary tissue of 2:1 was found after Photofrin and 4:1 after ALA. The results indicate that adjuvant intraoperative PDT may be a safe and effective method of destroying residual tumour, thereby preventing locoregional tumour recurrence.

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Mechanisms of Toxicity of Photoactivated Artificial Porphyrins Role of Porphyrin‐Protein Interactions

Cited by 21 publications

References 48 publications

A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin

A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin

Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus

Adjuvant intraoperative photodynamic therapy diminishes the rate of local recurrence in a rat mammary tumour model

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