Investigation of molecular mechanisms in photodynamic action and radiobiology with nanosecond flash photolysis and pulse radiolysis. Progress report, October 1, 1980-September 30, 1981
Laser flash photolysis experiments have led to a new mechanism for the ultraviolet photolysis of aqueous tryptophan (Trp), indole (Ind) and certain indole derivatives. Excitation at 265 nm leads to photoionization via a pre-fluorescent state with thermal activation. A new formula is proposed for predicting enzyme inactivation quantum yields. The predictions are in good agreement with measurements on six important enzymes at 254 nm and 280 nm. Kinetics models have been developed and tested for important stages in the photosensitization of DNA to near-ultraviolet radiation by furocoumarin compounds currently used for PUVA therapy (psoralen plus UV-A) of psoriasis and other human skin diseases. Experiments on photobinding of psoralen (Ps) and 8-methoxypsoralen (8-MOP) to calf thymus DNA are consistent with the assumption that equilibrium dark complexing of the furocoumarin to the DNA is a precondition for the formation of covalent monoadducts and cross-links. Singlet oxygen generation by furocoumarins has been investigated with liposomes and human erythrocytes (rbc). Results obtained with 3-carbethoxypsoralen (3-CPs), an experimental alternate PUVA sensitizer claimed to be non-tumorigenic, show that 3-CPs interacts with liposome and rbc membranes in the dark. Studies on photosensitization of egg lecithin liposomes by methylene blue (MB) incorporated in the membrane have led to the new result that membrane lysis is a two-stage process. The first stage induced by red light irradiation leads to membrane damage initiated by O/sub 2/*. Membrane lysis takes place in the dark, second stage under the action of mild hydrodynamic stress, such as slow gas bubbling.
- Research Organization:
- Illinois Inst. of Tech., Chicago (USA)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AS02-76EV02217
- OSTI ID:
- 6769186
- Report Number(s):
- DOE/EV/02217-38
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
TRYPTOPHAN
PHOTOLYSIS
DNA
PHOTOSENSITIVITY
PSORALEN
CHEMICAL REACTION KINETICS
CELL MEMBRANES
LIPOSOMES
LASERS
ULTRAVIOLET RADIATION
COUMARIN
PHOTOCHEMICAL REACTIONS
METHYLENE BLUE
AMINES
AMINO ACIDS
ANTI-INFECTIVE AGENTS
ANTICOAGULANTS
ANTIMICROBIAL AGENTS
AZINES
AZOLES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
CHLORIDES
CHLORINE COMPOUNDS
COUMARINS
DECOMPOSITION
DRUGS
ELECTROMAGNETIC RADIATION
ESTERS
HALIDES
HALOGEN COMPOUNDS
HEMATOLOGIC AGENTS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INDOLES
KINETICS
LACTONES
MEMBRANES
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANOIDS
PHENOTHIAZINES
PYRANS
PYRROLES
RADIATIONS
REACTION KINETICS
SENSITIVITY
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560111 - Radiation Effects on Biochemicals- In Vitro- (-1987)