Photosensitization of mitochondrial cytochrome c oxidase by hematoporphyrin derivative and related porphyrins in vitro and in vivo

Journal Article · Thu Sep 01 04:00:00 EDT 1983 · Cancer Res.; (United States)

OSTI ID:5744766

Gibson, S L; Hilf, R

Mitochondrial cytochrome c oxidase activity was inhibited by exposure to hematoporphyrin derivative followed by photoirradiation. Inhibition of enzyme activity in vitro was a dose- and time-related event, the log of percentage inhibition being linear with time. Exposure of mitochondria to hematoporphyrin or hydroxyethylvinyldeuteroporphyrin sensitized mitochondria to photoirradiation, whereas protoporphyrin IX was only weakly active as a photosensitizer for inhibition of cytochrome c oxidase. Mitochondria from mammary glands of pregnant rats showed hematoporphyrin-induced photosensitivity similar to those from R3230AC mammary adenocarcinomas. Mitochondria prepared from tumors of animals given injections of hematoporphyrin derivative in vivo and then photoirradiated in vitro demonstrated considerable sensitivity to light as reflected by significant inhibition of cytochrome c oxidase activity. A side by side comparison of hematoporphyrin derivative with hematoporphyrin, using this in vivo-in vitro experimental protocol, indicated that photosensitivity was retained for a longer time after treatment with hematoporphyrin derivative. Taken together, these data provide a potential mechanism of action, i.e., inhibition of respiration, for porphyrin-induced photosensitivity, and they offer a useful assay to investigate this family of therapeutic agents.

• Research Organization: Department of Biochemistry, University of Rochester School of Medicine and Dentistry, New York
• OSTI ID: 5744766
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 43:9; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

560114* -- Radiation Effects on Biochemicals-- In Animals-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BODY
CARBOXYLIC ACIDS
CARCINOMAS
CELL CONSTITUENTS
CELL CULTURES
CYTOCHROME OXIDASE
DEUTERIUM COMPOUNDS
DISEASES
ENZYME ACTIVITY
ENZYMES
GLANDS
HAEM DEHYDROGENASES
HEMATOPORPHYRINS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MAMMALS
MAMMARY GLANDS
METABOLIC ACTIVATION
MITOCHONDRIA
NEOPLASMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
PHOTOSENSITIVITY
PIGMENTS
PORPHYRINS
PREGNANCY
PROTOPORPHYRINS
RATS
RODENTS
SENSITIVITY
TRACER TECHNIQUES
VERTEBRATES