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Norwegian Radiation Protection Authority

Photosensitizing effects metalloporphyns in connection with hyperbilirubinemia

Terje Christensen, Gunnar Kinn and Jon B. Reitan

Radiation medicine department, Norwegian Radiation Protection Authority, and Institutes of Radiology and Pathology, Norwegian National Hospital, University of Oslo, Norway.

Paper
Abstract

Post address: Norwegian Radiation Protection Authority. P.O.Box 55, N-1345 Østerås, Norway, e-mail: nrpa@nrpa.no, Internet: http://www.nrpa.no

E-Mail: Terje.Christensen@nrpa.no, Gunnar.Kinn@nrpa.no, Jon.Reitan@nrpa.no
Norwegian Radiation Protection Authority:
nrpa@nrpa.no

Telephone: xx 47 67162500
Telefax: xx 47 22461304

Key words: Metalloporphyrins, porphyrins, phototherapy, bilirubin, light, DNA-damage, antioxidant, genotoxic effect.

Abstract

Metalloporphyrins have been suggested as chemotherapeutic agents in neonatal jaundice due to their inhibition of heme oxygenase. Human cells were treated with blue light in the presence of the metalloporphyrins tin-protoporphyrin, zinc-protoporphyrin, chromium-protoporphyrin and chromium-mesoporphyrin. The lamps used were of the same type as commonly used in the treatment of hyperbilirubinemia in newborns. The photodynamic effect of the metalloporphyrins on cellular DNA, and on cell survival, was compared. The induction of single strand breaks or alkali labile sites was measured by a method taking advantage of the selective fluorescence of the fluorochrome Hoechst 33258.

Zinc protoporphyrin induced more DNA-damage and cell death than tin protoporphyrin, probably due to a higher cellular uptake. The chromium-porphyrins did not induce photosensitization of DNA or photosensitized cell death. A small but significant photooxidation of tryptophan in the presence of chromium-porphyrins could be detected, but the effect was less than one tenth of the effect of light in the combination with tin-protoporphyrin, zinc-protoporphyrin, protoporphyrin and hematoporphyrin.

Bilirubin is known as an antioxidant, and it was of interest to see whether it could protect the cells from porphyrin-induced photodynamic damage. No protection by bilirubin from the cytotoxic effects of metalloporphyrins and light was observed.

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