The pH dependency of protoporphyrin IX formation in cells incubated with 5-aminolevulinic acid

Bech, Øystein; Berg, Kristian; Moan, Johan Emelian

doi:10.1016/s0304-3835(96)04558-2

Cited by 30 publications

(21 citation statements)

References 22 publications

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“…This leads to oxygen deficiency, enhanced glycolysis and low extracellular pH values, as is generally observed in tumors [9]. A low pH value in the tumors is in disfavor of PpIX formation, which, in cell cultures is found to decrease with decreasing pH values [10]. The lower activity of the PBGD enzyme at lower pH values [11] is in accordance with this observation.…”

Section: Discussionsupporting

confidence: 72%

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On the basis for tumor selectivity in the 5-aminolevulinic acid-induced synthesis of protoporphyrin IX

Moan

Akker

Juzenas

et al. 2001

J. Porphyrins Phthalocyanines

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When 5-aminolevulinic acid (ALA) is administered topically, intravenously or intraperitoneally to tumor-bearing animals or humans, tumor selective production of protoporphyrin IX (PpIX) is frequently observed. Several biophysical, biochemical and physiological factors explain this tumor selectivity, among which the most important ones seem to be: (1) a relatively high concentration of the rate-limiting enzyme porphobilinogen deaminase (PBGD) in tumors; (2) relatively low concentrations of ferrochelatase (FC) and iron in many tumors; (3) a slightly elevated tumor temperature, related to inflammation; and (4) a compromised barrier of the skin overlying tumors, leading to an increased penetration of ALA into tumors. All these factors are discussed in the present work and new data concerning the significance of the skin barrier and the tumor temperature are presented. It is shown that compromising the skin of mice by tape-stripping the stratum corneum leads to a strongly enhanced ALA penetration into the skin and even into the circulation. The skin overlying tumors (WiDr colon carcinoma tumors transplanted subcutaneously to mice) is also much more permeable to ALA than normal skin, even through no physical damage of the tumor skin can be seen. PpIX formation from ALA can be increased by increasing the temperature.

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Section: Discussionsupporting

confidence: 72%

“…The lifetime of a human erythrocyte is only 120 days. Thus, in a human body 10 11 erythrocytes need to be produced every day. This corresponds to 7.5 g hemoglobin, or 2 Â 10 18 heme groups.…”

Section: Introductionmentioning

confidence: 99%

On the basis for tumor selectivity in the 5-aminolevulinic acid-induced synthesis of protoporphyrin IX

Moan

Akker

Juzenas

et al. 2001

J. Porphyrins Phthalocyanines

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“…However, we did not observe any significant colour changes of the cells' media at the time they were harvested for the experiment. Studies reported by Bech et al (1997) and Wyld et al (1998) demonstrating that pH can affect PpIX synthesis were performed with cells that were exposed to different pH values during incubation with ALA. As mentioned in the Materials and Methods section, in our experiments the cells were incubated with fresh media 1 h before and during ALA incubation. Therefore, we do not suspect that any pH differences resulting from our tissue culture methods had a significant effect on PpIX production during this study.…”

Section: Discussionmentioning

confidence: 99%

“…Such studies have explored the role of ALA incubation time (Dietel et al, 1996;Krammer and Uberriegler, 1996;Gibson et al, 1997) and concentration (Krammer and Uberriegler, 1996;Gibson et al, 1997;Moan et al, 1998), cell type (Iinuma et al, 1994;Steinback et al, 1995;Wyld et al, 1997), cell cycle (Moan et al, 1998), proliferation status (Rebeiz et al, 1992;Schick et al, 1995;Momma et al, 1997), serum presence (Hanania and Malik, 1992;Fukuda et al, 1993), iron availability (Hanania and Malik, 1992;Iinuma et al, 1994;Rittenhouse-Diakun et al, 1995;Tan et al, 1997), pH (Bermudez Moretti et al, 1993;Krammer and Uberriegler, 1996;Bech et al, 1997;Wyld et al, 1998), glucose (Dietel et al, 1996), and temperature (Dietel et al, 1996). More detailed studies examined the effect of some of these factors on specific enzymes of the haem biosynthetic pathway (Schoenfeld et al, 1988;Gibson et al, 1998).…”

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confidence: 99%

Hypoxia significantly reduces aminolaevulinic acid-induced protoporphyrin IX synthesis in EMT6 cells

1999

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SummaryWe have studied the effects of hypoxia on aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) synthesis in EMT6 monolayer cultures characterized by different cell densities and proliferation rates. Specifically, after ALA incubation under hypoxic or normoxic conditions, we detected spectrofluorometrically the PpIX content of the following populations: (a) low-density exponentially growing cells; (b) high-density fed-plateau cells; and (c) high-density unfed-plateau cells. These populations were selected either for the purpose of comparison with other in vitro studies (low-density exponentially growing cells) or as representatives of tumour regions adjacent to (highdensity fed-plateau cells) and further away from (high-density unfed-plateau cells) capillaries. The amount of PpIX per cell produced by each one of these populations was higher after normoxic ALA incubation. The magnitude of the effect of hypoxia on PpIX synthesis was dependent on cell density and proliferation rate. A 42-fold decrease in PpIX fluorescence was observed for the high-density unfed-plateau cells. PpIX production by the low-density exponential cells was affected the least by ALA incubation under hypoxic conditions (1.4-fold decrease), whereas the effect on the high-density fed-plateau population was intermediate (20-fold decrease).

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“…Analysis of synthetic solutions of PpIX indicated that the non-invasive imaging system quantified PpIX in a similar manner to the Synergy HT plate reader (Figure 11 (36)(37)(38) rather than actual clinical application. However, the system described here can now be utilised to determine PpIX levels/changes in a non-invasive manner whilst therapeutic clinical dermatological PDT is in progress and as such is a useful advancement to the field.…”

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confidence: 96%

Validation of a non-invasive fluorescence imaging system to monitor dermatological PDT

Tyrrell

Campbell

Curnow

2010

Photodiagnosis and Photodynamic Therapy

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The pH dependency of protoporphyrin IX formation in cells incubated with 5-aminolevulinic acid

Cited by 30 publications

References 22 publications

On the basis for tumor selectivity in the 5-aminolevulinic acid-induced synthesis of protoporphyrin IX

On the basis for tumor selectivity in the 5-aminolevulinic acid-induced synthesis of protoporphyrin IX

Hypoxia significantly reduces aminolaevulinic acid-induced protoporphyrin IX synthesis in EMT6 cells

Validation of a non-invasive fluorescence imaging system to monitor dermatological PDT

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