Phototoxicity mechanism of a kryptocyanine dye in human red cell membranes and isolated murine mitochondria.

نویسندگان

  • O Valdes-Aguilera
  • G Ara
  • I E Kochevar
چکیده

The phototoxicity mechanism of a kryptocyanine dye, N,N'-bis(2-ethyl-1,3-dioxolane)kryptocyanine (EDKC+), has been studied in RBC membranes and isolated mitochondria. Lipophilic, positively charged dyes, such as EDKC+, may be useful as tumor-cell-selective, light-activated cytotoxic agents. Exposure of the RBC membranes to 700-nm light and EDKC+ inhibited membrane acetylcholinesterase and photodecomposed EDKC+ in air-purged but not argon-purged samples. Photoinactivation of acetylcholinesterase was the same in D2O as in H2O and was not quenched by superoxide dismutase. Ascorbate and azide (10 mM) quenched or slightly enhanced, respectively, the inactivation. In argon-purged samples containing methyl viologen, EDKC+ photodecomposed, but acetylcholinesterase activity was unaffected. The mechanism may involve electron transfer to oxygen and subsequent formation of toxic photoproducts from EDKC+. In contrast, exposure of murine mitochondria to EDKC+ and 700-nm light caused inhibition of mitochondrial respiration in both the presence and absence of oxygen. The photodecomposition of EDKC+ correlated with inhibition of respiration. Thus, the phototoxicity of EDKC+ in mitochondria may be due to electron transfer from photoexcited EDKC+ to oxygen and electron acceptors in the membrane. These studies indicate that dyes such as EDKC+ may be useful for photochemotherapy of hypoxic regions in tumors.

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عنوان ژورنال:
  • Cancer research

دوره 48 23  شماره 

صفحات  -

تاریخ انتشار 1988