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Biomedical subjects

J Moan

Publications and source records attributed to J Moan.

At least 127 records · Page 7Linked to original sources
PubMed1991

Sensitizer for photodynamic therapy of cancer: a comparison of the tissue distribution of Photofrin II and aluminum phthalocyanine tetrasulfonate in nude mice bearing a human malignant tumor.

The distribution of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in tissues of BALB/c nu/nu nude mice bearing the LOX human melanoma was measured fluorimetrically at different times after intraperitoneal injection of the drugs, 20 mg/kg body weight. The plasma levels of the drugs as well as the excretion in feces and urine were also determined. The plasma concentrations of both drugs were found to build up in a similar manner during the first 30 min after injection. Thereafter, the plasma level of AIPCS4 decreased exponentially with an elimination half-life of 1.5 hr. The kinetics of elimination of P-II from the plasma were consistent with a 2-compartment model, with 90% of sensitizer lost with a half-life of about 5 hr, and the remaining fraction with a half-life of 30 hr. About 80% of the injected dose of P-II was excreted in the feces during the 7-days following injection, while 77% of AIPCS4 was excreted in the urine during the same period. After injection of a dose of 20 mg/kg, the concentrations of P-II in the LOX tumor as well as in the skin, muscle, brain, heart, lung, kidney and liver increased for about 24 hr, then remained constant or decreased slowly for the next 48 hr, after which they decreased slightly faster. On the other hand, the concentrations of APICS4 in most tissues as well as in the tumor peaked at about 30 min, then decreased with a half-life of between 1.5 and 3 hr. The tumor/skin concentration ratio was about 1 for both drugs (1-24 hr after injection). The tumor/muscle concentration ratio was about 2 for P-II at all sampling times, and maximally 10 (at 18 hr after injection) for AIPCS4. In the present tumor model, the tumor/tissue concentration ratio for all tissues at 1 hr and at 24 hr after the injection was equal for the 2 drugs or higher for AIPCS4.

Animals↗
PubMed1991

Interaction of cremophor EL with human plasma.

1. Interaction of cremophor EL (CRM) with human plasma lipoproteins and nonlipoproteins has been investigated by ultracentrifugation. 2. VLDL has only a low or negligible capacity to bind CRM, i.e. there is little or no change in the optical absorption at 280 nm of VLDL when CRM is added. 3. A low density subfraction of low density lipoproteins seems to associate substantially with CRM at relatively low CRM concentrations (1-3 mg/ml), but such association is not evident for CRM concentrations in the region 12-116 mg/ml. 4. Low density lipoproteins (LDL) may act as a carrier for CRM-emulsions, yet there seems to be no concomitant change in the 280 nm optical absorption of the proteins of LDL. 5. The position in the gradient (i.e. in the centrifugation tube after centrifugation) of high density lipoproteins (HDL) is shifted towards lower density in the presence of 1-4 mg CRM/ml. For higher concentrations of CRM, a destruction of HDL can be observed: the HDL distribution is converted into a bimodal distribution of respectively lighter and heavier "HDL"-particles than the normal ones; the densities at the peaks of these distributions are approximately 1.07 g/ml (light), 1.20 g/ml (heavy) and 1.11 g/ml (normal HDL). The optical extinction coefficient is apparently the same for the proteins of normal--and modified HDL. 6. Even high CRM concentrations (less than or equal to 116 mg/ml) have no perceptible effect on the gradient positions and profile of human serum albumin (HSA) and/or other heavy proteins. 7. The possible biological significance of these findings is briefly touched upon.

Emulsions↗
PubMed1991

The temperature sensitivity of the Robertson-Berger sunburn meter, model 500.

The temperature dependency of the response of the Robertson-Berger sunburn detector was tested. Exposure to ultraviolet radiation (UVR) at 254, 302 and 315 nm resulted in temperature coefficients of -6.8%, +4.3% and +14.6% per 10 degrees C respectively. Scans of the spectral response curve showed a redshift with increasing temperatures in accordance with measurements of the temperature response at solar exposure. The temperature dependency during solar exposure was calculated as S(T) = (0.831 +/- 0.060) 10(-2)T + (0.694 +/- 0.004), relative to a detector kept at a constant temperature, 32 degrees C. The difference in average summer temperatures for Oslo city in the period 1951-1989 would influence uncorrected annual Robertson-Berger counts similarly as an approximate 2% change in the total amount of atmospheric ozone. The variation of the sensitivity of the Robertson-Berger meter with temperature is recommended to be corrected for by simultaneous temperature registrations.

Hot Temperature↗
PubMed1991

The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen.

NHIK 3025 cells were incubated with Photofrin II (PII) and/or tetra (3-hydroxyphenyl)porphyrin (3THPP) and exposed to light at either 400 or 420 nm, i.e. at the wavelengths of the maxima of the fluorescence excitation spectra of the two dyes. The kinetics of the photodegradation of the dyes were studied. When present separately in the cells the two dyes are photodegraded with a similar quantum yield. 3THPP is degraded 3-6 times more efficiently by light quanta absorbed by the fluorescent fraction of 3THPP than by light quanta absorbed by the fluorescent fraction of PII present in the same cells. The distance diffused by the reactive intermediate, supposedly mainly 1O2, causing the photodegradation was estimated to be on the order of 0.01-0.02 micron, which corresponds to a lifetime of 0.01-0.04 microsecond of the intermediate in the cells. PII has binding sites at proteins in the cells as shown by an energy transfer band in the fluorescence excitation spectrum at 290 nm. During light exposure this band decays faster than the Soret band of PII under the present conditions. Photoproducts (1O2 etc.) generated at one binding site contribute significantly in the destruction of remote binding sites.

Biodegradation, Environmental↗
PubMed1991

Light induced relocalization of sulfonated meso-tetraphenylporphines in NHIK 3025 cells and effects of dose fractionation.

Human cervix carcinoma cells of the line NHIK 3025 were incubated for 18 h with sulfonated meso-tetraphenylporphines (TPPSn where n = 1, 2a, 2o or 4) followed by 1 h in sensitizer-free medium and then exposed to light. The fluorescing fraction of TPPS4, TPPS2o and TPPS2a has recently been shown to be located intracellularly in extracellular granules which are intracellularly localized in a similar pattern as acridine orange-stained granules, assumed to be endosomes and lysosomes (Berg, K., A. Western, J. Bommer and J. Moan. Photochem. Photobiol. 52, 481-487). Light exposure induced a relocalization of TPPS4 from its granular pattern to mainly the nuclear area while TPPS2o and TPPS2a relocalized mainly to cytoplasmic areas. After the light-induced relocalization TPPS4 became less efficient in sensitizing photoinactivation of cells as measured per fluorescing cellbound TPPS4 molecules while TPPS2a and TPPS2o became more efficient. These changes were independent of the extracellular concentration of TPPSn applied to the cells, except for cells incubated with 75 micrograms/mL TPPS4. These cells became more sensitive to light after a light exposure inactivating 20% of the cells. This increased photosensitivity seems to be related to a 2-2.5 fold increase in the amount of fluorescing cellbound TPPS4 induced by the first light exposure.

Biological Transport↗
PubMed1990

Aluminum phthalocyanines with asymmetrical lower sulfonation and with symmetrical higher sulfonation: a comparison of localizing and photosensitizing mechanism in human tumor LOX xenografts.

A comparison of time-dependent localization patterns between lower, asymmetrical (AIPCS2a) and higher, symmetrical (AIPCS4) sulfonates of aluminum phthalocyanines in human malignant melanoma LOX transplanted to athymic nude mice from 1 to 120 hr after i.v. administration was made by means of laser scanning fluorescence microscopy. The lipophilic AIPCS2a was distributed mainly in tumor cells, while the hydrophilic AIPCS4 localized only in the vascular stroma of the tumor tissue. Concomitantly, comparative observations on the killing mechanism of photodynamic effects after treatment with a much lower i.v. dose of AIPCS2a and AIPCS4 plus laser light on the human tumor LOX were also made by morphological studies. Light and electron microscopy showed that there was a direct, extensive, photo-damaging action on all organelles and nuclear structure in the tumor cells after PDT with AIPCS2a; whereas the photo-induced injury to the tumor tissue after treatment with AIPCS4 and light was largely the consequence of initial functional vasogenic response and ultimate damage to vascular structure. These findings correlate well with the different localization patterns of the 2 dyes observed in human tumor tissues.

Animals↗
PubMed1990

The lengths of DNA fragments light-induced in the presence of a photosensitizer localized at the nuclear membrane of human cells.

DNA damage was apparently introduced selectively in the parts of DNA localized close to the nuclear membrane of human NHIK 3025 cells. This was obtained by illumination of the cells in the presence of a hydrophobic photosensitizer, Photofrin II, which was located in membrane structures but not in the nucleus. Photofrin II sensitizes DNA to light mainly via singlet oxygen, which diffuses about 0.1 microns in its intracellular lifetime. By measuring DNA unwinding in alkali after illumination or X-irradiation of cells, the distribution of the number of DNA bases between two adjacent, photodamaged DNA sites was estimated. The average length of these DNA fragments was found to be 155 kilobases (kb).

DNA↗
PubMed1990

Localization of fluorescent Photofrin II and aluminum phthalocyanine tetrasulfonate in transplanted human malignant tumor LOX and normal tissues of nude mice using highly light-sensitive video intensification microscopy.

A comparative kinetic observation of the in vivo biolocalization of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in a transplanted human malignant tumor LOX and in normal tissues of nude mice has been made by means of highly light-sensitive video intensification microscopy at various intervals after i.p. administration. In the human tumor LOX, transplanted to athymic nude mice, fluorescence of P-II was observed on the membrane and in the cytoplasm of tumor cells, and in the stroma 4-48 hr post-injection. From 72 hr post-injection almost all fluorescing P-II had disappeared from the membrane of the tumor cells while strong fluorescence was still found in the stroma. AIPCS4 fluorescence was seen mainly in tumorous stroma with none detected in the tumor cells. Almost no fluorescence was found in the tumorous stroma 24 hr after injection. In most normal tissues observed, P-II was eliminated at a much slower rate than AIPCS4, but the in vivo biolocalization of the 2 drugs was similar. They were observed primarily where collagenous proteins are normally found, i.e. basal lamina, collagenous connective tissue, and in keratinized epithelium, renal epithelium, mononuclear phagocyte system and on the membrane of muscular cells. In addition, AIPCS4 had a strong affinity for the bronchiogenic epithelium. In the skin, P-II was distributed in keratinized epithelium, hair, hair follicles and their accessory, collagenous connective tissue of dermis, whereas AIPCS4 was present only in hair and collagenous connective tissue of dermis. No fluorescence of P-II or of AIPCS4 was found in the skin epidermis, nor in the transitional epithelium of the bladder mucosa.

Animals↗
PubMed1990

Hematoporphyrin diethers--V. Plasma protein binding and photosensitizing efficiency.

1. Binding of added hematoporphyrin (HP) ethers to human plasma proteins and lipoproteins has been investigated by ultracentrifugation. 2. The binding to low density lipoproteins (LDL) has been discussed in terms of photosensitized tumor growth delay of tumors and HPLC-retention time, i.e. degree of polarity. 3. The LDL-binding data show a uniform relationship to sensitizing efficiency and degree of polarity, the only exception being HP-diamyl ether. No such uniform relationship exists for less related dyes, such as HP, tetraphenylporphyrin tetrasulfonate and HP-dimethyl ether.

Animals↗
PubMed1990

Localization of potent photosensitizers in human tumor LOX by means of laser scanning microscopy.

By means of laser scanning fluorescence microscopy the intratumoral localization patterns of several photosensitizers in LOX tumors in nude mice were studied. Lipophilic dyes such as P-II (Photofrin II), 3-THPP tetra(3-hydroxyphenyl)porphin, TPPS1 (tetraphenylporphine monosulfonate), TPPS2a (tetraphenylporphine disulfonates with the sulfonate groups on adjacent rings), A1PCS1 (aluminium phthalocyanine monosulfonate) and A1PCS2 (aluminium phthalocyanine disulfonates) localized mainly in tumor cells. The fluorescence intensity of these dyes increased from 4 h to 48 h post-injection and the fluorescence was still observable 120 h post-injection. The more hydrophilic dyes such as TPPS2o (tetraphenylporphine disulfonates with the sulfonates groups on opposite rings), TPPS3 (tetraphenylporphine trisulfoantes), TPPS4 (tetraphenylporphine tetrasulfonates), A1PCS3 (aluminium phthalocyanine trisulfonates) and A1PCS4 (aluminium phthalocyanine tetrasulfonates) localized mainly extracellularly in the tumorous stroma. The fluorescence intensity of these dyes decreased from 4 h to 48 h post-injection. 120 h post-injection no significant fluorescence of these dyes could be seen in the tumors. The data are discussed in relation to what is known about the in vivo photosensitizing efficiency of some of the dyes.

Animals↗
PubMed1990

Water-soluble metal naphthalocyanines--near-IR photosensitizers: cellular uptake, toxicity and photosensitizing properties in NHIK 3025 human cancer cells.

Metal naphthalocyanine complexes (MNCSs) absorb light in the near-IR spectral region (760 nm) where tissue penetration is optimal and they have been proposed as agents for photodynamic therapy (PDT). Sulphonated derivatives of tris-(2,3-naphthalocyanato) bis-chloroaluminium(III) and zinc(II) with various degrees of sulphonation were prepared. Cellular uptake, aggregation in cellular environments, cytotoxicity and photosensitizing properties were studied. Three of the four dyes studied were taken up by cells to a satisfactory degree and were not cytotoxic at the concentration used (10 micrograms ml-1). The least sulphonated sample of zinc naphthalocyanine produced some phototoxic effects (LD50 = 1.12 J cm-2). All the other samples of sulphonated naphthalocyanine were found to be aggregated inside the NHIK 3025 cells, preventing any significant PDT effect.

Biological Transport, Active↗
PubMed1990

Cellular inhibition of microtubule assembly by photoactivated sulphonated meso-tetraphenylporphines.

This work relates to studies on modes of phototoxicity by sulphonated mesotetraphenylporphines on cultured cells. Toxicity appears to be related to inhibition of microtubule function. Treatment of human cervix carcinoma cells of the line NHIK 3025 incubated for 18 h with meso-tetraphenylporphine sulphonates (TPPSn where n = 2a, 2o or 4) and exposed to light, inhibits multiplication for the first hours after light exposure, a significant fraction of the cells accumulating in mitosis. The maximal number of cells in mitosis after treatment (approximately 20%) is dependent on the fluence but is similar for all three photosensitizers. For the first hours after treatment the mitotic cells were always mainly in metaphase; mainly seen as c-metaphases and three-group metaphases. During this time anaphase and telophase cells were absent or greatly reduced in number. Indirect immunofluorescence staining of beta-tubulin showed that the spindle apparatus of mitotic cells was perturbed in all cases. Results are presented which indicate that photoactivation of TPPSn located on the plasma membrane destroys microtubules in interphase cells and leads to arrest of the cells in mitosis. The localization of the dye which sensitizes the photoinduced perturbation of microtubules is further discussed.

Cell Division↗
PubMed1990

Phthalocyanine fluorescence in tumors during PDT.

Athymic nude mice with human tumors transplanted to one of the hind legs were given aluminium phthalocyanine disulfonate (AlPcS2) intraperitoneally. Twenty-four hours after the injection the mice were placed with the tumor in the sample position in a fluorescence spectrometer with modulated excitation. Exposure of the tumors to laser light at a fluence rate of 50-200 mW/cm2 led to a rapid transient reduction by up to 50% of the phthalocyanine fluorescence of the tumor. After the laser irradiation the fluence rate of the fluorescence increased almost up to the initial value within a few minutes. This finding should be taken into account when optimal fluence rates and dose fractionation schemes are sought for photodynamic therapy.

Animals↗
PubMed1990

Intracellular localization of sulfonated meso-tetraphenylporphines in a human carcinoma cell line.

The intracellular localization of meso-tetraphenylporphines sulfonated to different degrees (TPPSn), in a human cervix carcinoma cell line (NHIK 3025), was studied by fluorescence microscopy and fluorescence spectroscopy. After an 18 h incubation, TPPS4, TPPS2a and TPPS2o were localized in extranuclear granules. Studies of cells stained with both TPPS4, and acridine orange, which is known to fluoresce red in lysosomes, indicated that these granules were lysosomes. In addition, a fraction of the cellbound TPPS4, TPPS2a and TPPS2o seems to be associated with the plasma membrane. Fluorescence quenching studies of cells doublestained with acridine orange and TPPS4 indicated that TPPS4 is also localized in the nucleus and in the extralysosomal cytoplasm. The intracellular location of TPPS1 differed from that of the other TPPSns studied: In 6 out of 9 experiments fluorescing extranuclear granules were found. A diffuse fluorescence extending from the perinuclear area was also observed.

Biological Transport↗
PubMed1990

Annual exposures to carcinogenic radiation from the sun at different latitudes and amplification factors related to ozone depletion. The use of different geometrical representations of the skin surface receiving the ultraviolet radiation.

In most calculations of annual fluences of carcinogenic light as well as of the radiation amplification factor and of biological amplification factors associated with ozone depletions, the radiation is assumed to fall on a horizontally oriented plane surface. This is obviously a bad approximation of the surface of the human body. In order to evaluate the importance of using a realistic geometric representation of the surface of the human body we here present calculations of the flux of carcinogenically effective radiation falling on three different bodies: a vertically standing cylinder, a sphere and a horizontally oriented surface. The exposure to carcinogenic radiation depends strongly on the surface geometry. However we find that the radiation amplification factors are almost independent of the surface geometry chosen. The biological amplification factors for the three geometrical representations are also similar to within 20%. The total amplification factor for the increase in the incidence of non-melanoma skin cancer related to ozone depletion is about 17% larger when a cylindrical representation is used compared to when a plane horizontal surface is considered.

Humans↗