Role of active oxygen species in the photodestruction of microsomal cytochrome P-450 and associated monooxygenases by hematoporphyrin derivative in rats
The cytochrome P-450 in hepatic microsomes prepared from rats pretreated with hematoporphyrin derivative was shown to be rapidly destroyed in the presence of long-wave ultraviolet light. The photocatalytic destruction of the heme-protein was dependent on both the dose of ultraviolet light and of hematoporphyrin derivative administered to the animals. The destructive reaction was accompanied by increased formation of cytochrome P-420, loss of microsomal heme content, and diminished catalytic activity of cytochrome P-450-dependent monooxygenases such as aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase. The specificity of the effect on cytochrome P-450 was confirmed by the observation that other heme-containing moieties such as myoglobin and cytochrome c were not susceptible to photocatalytic destruction. The destruction of cytochrome P-450 was a photodynamic process requiring oxygen since quenchers of singlet oxygen, including 2,5-dimethylfuran, histidine, and beta-carotene, each substantially diminished the reaction. Scavengers of superoxide anion such as superoxide dismutase and of H/sub 2/O/sub 2/ such as catalase did not protect against photodestruction of cytochrome P-450, whereas inhibitors of the hydroxyl radical, including benzoate, mannitol, and ethyl alcohol, did afford protection. These results indicate that lipid-rich microsomal membranes and the heme-protein cytochrome P-450 embedded therein are potential targets of injury in cells exposed to hematoporphyrin derivative photosensitization.
- Research Organization:
- Case Western Reserve Univ., Cleveland, OH
- OSTI ID:
- 5708137
- Journal Information:
- Cancer Res.; (United States), Vol. 45:2
- Country of Publication:
- United States
- Language:
- English
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CYTOCHROMES
BIOLOGICAL RADIATION EFFECTS
PHOTOLYSIS
HEMATOPORPHYRINS
RADIOSENSITIVITY EFFECTS
OXYGENASES
DOSE-RESPONSE RELATIONSHIPS
FURANS
HEME
HISTIDINE
HYDROGEN PEROXIDE
LIVER
MICROSOMES
MYOGLOBIN
OXYGEN
PHOTOSENSITIVITY
RATS
SUPEROXIDE DISMUTASE
ULTRAVIOLET RADIATION
AMINO ACIDS
ANIMALS
AZOLES
BIOLOGICAL EFFECTS
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
DECOMPOSITION
DIGESTIVE SYSTEM
ELECTROMAGNETIC RADIATION
ELEMENTS
ENZYMES
GLANDS
GLOBIN
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
IMIDAZOLES
MAMMALS
NONMETALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEROXIDES
PHOTOCHEMICAL REACTIONS
PIGMENTS
PORPHYRINS
PROTEINS
RADIATION EFFECTS
RADIATIONS
RODENTS
SENSITIVITY
VERTEBRATES
560111* - Radiation Effects on Biochemicals- In Vitro- (-1987)