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.
Post address: Norwegian Radiation Protection Authority.
P.O.Box 55, N-1345 Østerås, Norway, e-mail: firstname.lastname@example.org,
Norwegian Radiation Protection Authority: email@example.com
Telephone: xx 47 67162500
Telefax: xx 47 22461304
Key words: Metalloporphyrins, porphyrins, phototherapy,
bilirubin, light, DNA-damage, antioxidant, genotoxic effect.
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.