Mechanistic investigation of doxycycline photosensitization by picosecond-pulsed and continuous wave laser irradiation of cells in culture

Journal Article · Sun Apr 15 04:00:00 UTC 1990 · Journal of Biological Chemistry; (USA)

OSTI ID:6904647

Shea, C R; Hefetz, Y; Gillies, R; Wimberly, J; Dalickas, G; Hasan, T ^[1]

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1. Massachusetts General Hospital, Boston (USA)

In order to elucidate the photophysical mechanisms of cellular phototoxicity sensitized by doxycycline, MGH-U1 human bladder carcinoma cells in vitro were treated with 20.7 microM doxycycline and irradiated with either a pulsed (lambda = 355 nm, pulse duration = 24 ps) or a continuous wave (lambda = 351 nm) laser. Cumulative radiant exposure and irradiance were systematically varied in experiments with both lasers. Phototoxicity was assessed by epifluorescence microscopy of unfixed cells using rhodamine 123 labeling of mitochondria. With the continuous wave source, the cumulative radiant exposure required for induction of phototoxic injury was independent of irradiance. With the 24-ps-pulsed source, a significantly lower cumulative radiant exposure was required to induce the phototoxicity when the peak irradiance was 5.8 x 10(7) or 1.3 x 10(8) watts cm-2 compared with when peak irradiance was either lower (6.0 x 10(6) watts cm-2) or higher (7.6 x 10(8) watts cm-2). The measured fluorescence lifetimes of doxycycline in buffered saline solution were longer than the laser pulse duration of 24 ps. The increased efficiency of photosensitization at the optimal peak irradiance in the ps domain appears to result from sequential multiphoton absorption involving higher excited states of the singlet manifold. At the highest irradiance studied, on the other hand, reduced efficiency of photosensitization is attributed to increased photodegradation of doxycycline from higher excited states by processes such as photoionization. A model consistent with these observations is presented along with calculations, based on simple rate equations, that fit the essentials of the proposed model.

• OSTI ID: 6904647
• Journal Information: Journal of Biological Chemistry; (USA), Journal Name: Journal of Biological Chemistry; (USA) Vol. 265:11; ISSN JBCHA; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

560400* -- Other Environmental Pollutant Effects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOLOGICAL EFFECTS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL CULTURES
CHEMICAL REACTIONS
DECOMPOSITION
DRUGS
DYES
ELECTROMAGNETIC RADIATION
FLUORESCENCE
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
LASER RADIATION
LASERS
LUMINESCENCE
MAMMALS
MAN
MITOCHONDRIA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
PHOTOCHEMICAL REACTIONS
PHOTOLYSIS
PRIMATES
RADIATIONS
REAGENTS
RHODAMINES
SENSITIVITY
TUMOR CELLS
VERTEBRATES