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Biomedical subjects

J Moan

Publications and source records attributed to J Moan.

At least 145 records · Page 8Linked to original sources
PubMed1990

Ultraviolet-radiation and skin cancer. Effect of an ozone layer depletion.

The effect of changes in the ozone layer on the incidence of skin cancer was explored using data for Norway. Attempts were made to arrive at a relationship between the "environmental effective UV-dose" and the skin cancer incidence. Norway is well suited for this purpose because of the large variation in the annual UV-dose from north to south. Furthermore we have a well developed cancer registry and a homogeneous population with regard to skin type. Four different regions of the country, each with a broadness of 1 degree in latitude (approximately 111 km), were selected (located around 69.5, 63.5, 60 and 58.5 degrees N). The annual effective UV-doses for these regions were calculated, assuming normal ozone conditions throughout the year and the action spectrum proposed by CIE, which extends up to 400 nm. The incidence rate (in the period 1970-1980) of malignant melanoma and non-melanoma skin cancer (mainly basal cell carcinoma) increased with the annual environmental UV-doses. For both these types of cancer a quadratic dose-effect relationship seems to be valid to a first approximation. The present data indicate that the incidence of skin cancer would increase by approximately 2% for each percent ozone reduction.

Humans↗
PubMed1990

A comparison of three photosensitizers with respect to efficiency of cell inactivation, fluorescence quantum yield and DNA strand breaks.

Intracellular properties of three photosensitizers relevant to photodynamic cancer therapy were compared using cultured human NHIK 3025 cells. When taken up in the cells, the hydrophilic photosensitizer aluminum phthalocyanine tetra sulfonate required about 10 times more quanta of light absorbed per cell to kill 90% of the cells than did the hydrophobic dyes Photofrin II and tetra(3-hydroxyphenyl)porphyrin. In spite of this, the phthalocyanine molecule was the most efficient dye per quantum of excitation light, since the extinction coefficient of the phthalocyanine is more than 10 times higher than that of the two hydrophobic photosensitizers at therapeutic wavelengths. The two hydrophobic dyes had significantly higher fluorescence quantum yields when taken up by cells than when bound to human plasma or human serum albumin, whereas the opposite was true for the hydrophilic phthalocyanine dye--suggesting intracellular aggregation. Finally, the potential genetic toxicities of the drugs in the form of DNA strand breaks were compared. The aluminum phthalocyanine tetra sulfonate photosensitized more DNA strand breaks than did Photofrin II and tetra(3-hydroxyphenyl)porphyrin when compared at the same level of cell survival.

Cell Survival↗
PubMed1990

Cellular uptake and relative efficiency in cell inactivation by photoactivated sulfonated meso-tetraphenylporphines.

The cellular uptake, relative fluorescence quantum yields and photosensitizing efficiencies of meso-tetraphenylporphines sulfonated to different degrees (TPPSn) have been investigated using the human carcinoma cell line NHIK 3025. The efficiencies of these dyes in photoinactivation of cells were highly dependent on the number of sulfonate groups on the derivatives. These differences in phototoxicity were primarily due to different abilities to be taken up by cells, but were also dependent upon the cellular localization of the dyes. TPPS1 and TPPS2a were more efficiently taken up by the cells than TPPS2o and TPPS4. Plasma membrane associated TPPS4 was less efficient in cell inactivation per quantum of fluorescence emitted than intracellularly located dye. This was also to some extent the case for TPPS1 but not for TPPS2a and TPPS2o. The results presented here indicate that TPPS2a and TPPS1 are the most promising of the TPPSns for possible future use in photodynamic therapy.

Cell Survival↗
PubMed1989

Biological amplification factor for sunlight-induced nonmelanoma skin cancer at high latitudes.

Data for the incidence of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin, registered for six regions of Norway during 10 years (1976-1985), were used to evaluate the biological amplification factor Ab for induction of these cancers by sunlight. Ab is the ratio of the increment in skin cancer production to the increment in causative sunlight exposure. Two different approximations were used for the action spectrum for carcinogenesis: an erythema action spectrum; and an action spectrum for mutagenesis of cells in the basal layer of the skin. These two fundamentally different approaches yielded Ab values that were similar to within about 10%: 2.1-2.3 for BCCs; and 1.6-1.8 for SCCs. Using a radiation amplification factor for ozone depletion of 0.8-1.1, we find that the total amplification factor for BCCs is within the range 1.6-2.1 and that that for SCCs is within the range 1.3-1.7 at northern latitudes of 60-70 degrees. Thus, an ozone depletion of 1% will result in an increase in the incidence of BCCs by 1.6-2.1% and of SCCs by 1.3-1.7%. There were no significant differences between the values for men and women. Neither was there any significant difference between Ab values found for skin commonly exposed to sunlight (face) and for skin sites normally covered by clothes and therefore receiving much lower exposures, in spite of the fact that the tumor density per unit skin area was a factor of 20 or more larger at the former sites. This observation, as well as the curves relating cancer incidence with annual exposure to carcinogenic sunlight, supports a power law relationship between cancer incidence and annual sun exposure. Sunlight appears to be the main cause of BCCs and SCCs even at the high latitudes of Northern Norway. All over, BCCs were found to be about 6 times more frequent than SCCs. The ratio of the incidence of BCCs to that of SCCs seemed to be independent of the latitude. Finally, BCCs were found to be equally frequent among men and women, while SCCs were found to be about twice as frequent among men as among women.

Basal Cell Carcinoma↗
PubMed1989

Ozone depletion and its consequences for the fluence of carcinogenic sunlight.

A slight reduction of the ozone level over the northern hemisphere in the period 1969-1986 has been reported [D. Lindley, Nature (Lond.), 323: 293, 1988]. Ozone measurements performed in Oslo are in agreement with this. However, the ozone level for 1987 and 1988 was above normal, and no negative or positive trend is apparent for the last 10 years. The consequences of an ozone reduction for the fluence rate of carcinogenically effective sunlight was evaluated on the basis of recent action spectra for mutagenesis in cells, carcinogenesis in mice, and erythema induction in humans. Depending on the choice of action spectrum we find amplification factors (defined as percentage increase in yearly fluence of carcinogenically efficient sunlight per percentage reduction of the ozone level) between 1.1 and 1.3 at latitudes between 0 and 20 degrees and between 0.9 and 1.1 for Northern Europe. These estimates are significantly lower than 2.0, which is the value found when the calculations are based on the DNA absorption spectrum (R. B. Setlow, Proc. Natl. Acad. Sci. USA, 71:3363-3366, 1974).

Animals↗
PubMed1989

Intracellular localization of photosensitizers.

The intracellular localization of photosensitizers can be studied by different methods. One method involves homogenization of the cells followed by differential ultracentrifugation which leads to fractions enriched in nuclear, mitochondrial, and microsomal material as well as a supernatant fraction. More detailed information can be obtained by electron microscopy of cells exposed to light in the presence of photosensitizers. This method is based on the assumption that damage is primarily induced at intracellular sites where the concentration of photosensitizer is high. By irradiating the cells at 6 degrees C, where biochemical reactions are slow, and then incubating them for different times at 37 degrees C, it is possible to follow the development of damage. The amount of photosensitized damage to enzymes or cell functions whose localization in the cells is known gives information about the intracellular localization of the sensitizer. Fluorescence microscopy is the most direct method and is widely applicable because most photosensitizers fluoresce. Lipophilic dyes generally localize in membrane structures. In future more attention should be paid to the localization of dyes in lysosomes, as suggested by early reports. Mitochondria, the endoplasmic reticulum and nuclear membrane are other important loci for intracellular localization of sensitizers.

Animals↗
PubMed1989

Evaluation of sulfonated aluminum phthalocyanines for use in photochemotherapy. Cellular uptake studies.

Cellular uptake of aluminum phthalocyanine sulfonated to different degree was studied by means of fluorescence measurements and HPLC chromatography. These results were correlated to the lipophilic property of each drug measured as the distribution of the drug between a lipophilic phase (Triton X-114) and an aqueous phase. All the sulfonated aluminum phthalocyanines were taken up into cells to a higher extent than porphyrins of a similar lipophilicity. The cellular uptake of monosulfonated aluminum phthalocyanine was 10-fold higher than the cellular uptake of tetrasulfonated aluminum phthalocyanine and at least 50% higher than tetra(3-hydroxy-phenyl)porphin which is so far the porphyrin shown to be taken up into cells to the highest extent.

Cells, Cultured↗
PubMed1989

Effects of UV radiation of cells.

UV radiation interacts with mammalian cells in a very complex manner, although DNA appears to be the main chromophore. Recent literature within this field is reviewed. The review is concentrated on the following main topics: Chromophores for UV action, photoproducts in DNA, repair of UV-induced DNA damage, wavelength interactions, inactivation, mutagenesis, transformation and protection mechanisms against UV damage.

Animals↗
PubMed1989

The distribution of porphyrins with different tumour localising ability among human plasma proteins.

The distribution among the main fractions of human plasma lipoproteins of a number of porphyrins with different tumour localising ability has been determined by means of ultracentrifugation. A main trend is that the fraction of the dyes that are bound to low density lipoprotein (LDL) increases, and the fraction bound to HSA decreases with decreasing polarity of the dyes. An asymmetric charge distribution, such as in TPPS2a, favours LDL-binding more than expected on the basis of lipophilicity. No correlation between the known tumour localising ability of the drugs tested in the present work and their relative affinity for LDL was found. One of the best tumour localisers reported in the literature, TPPS4, hardly binds to LDL, while Hp and Pp, which are commonly considered inefficient tumour localisers, do have a significant affinity for LDL. On the other hand, the LDL binding capacity for a drug is suggested to be a good index for cellular uptake. Such an index does not necessarily imply that the actual uptake occurs by the LDL pathway.

Blood Proteins↗
PubMed1989

Evaluation of sulfonated aluminum phthalocyanines for use in photochemotherapy. A study on the relative efficiencies of photoinactivation.

The cellular photosensitivity caused by aluminum phthalocyanines sulfonated to different degrees (AlPcSn) has been investigated. The phototoxic effect increased with decreasing number of sulfonate groups on the macrocycle, with the exception of AlPcS1 which was less phototoxic than AlPcS2 but more phototoxic than AlPcS3 and AlPcS4. The tendency of the AlPcSns to aggregate in our cellular system increased with increasing lipophilicity of the sensitizers. The aggregates had little or no photosensitizing activity. The low efficiency of cell inactivation caused by AlPcS1 can be explained by the highly aggregated state of this sensitizer in the cells. AlPcS2 and AlPcS3 induced a lower degree of cell inactivation per fluorescing quantum and per quantum absorbed by monomeric species than did AlPcS2 and AlPcS1. AlPcS4 and AlPcS3 are therefore suggested to be in different intracellular locations than AlPcS2 and AlPcS1.

Cells, Cultured↗
PubMed1989

Preparation and photosensitizing properties of hematoporphyrin ethers.

Hematoporphyrin ethers having acyl or aryl substituents in the 2 and 4 positions of the porphyrin ring have been synthesized, starting from protoporphyrin HBr adduct, and tested for photosensitizing efficiency on cells in vitro and transplanted tumors in mice. In general, they resemble the tumor localizing fraction of hematoporphyrin derivative (Hpd). Cellular uptake and retention runs parallel with the degree of their non-polarity and in vitro sensitizing efficiencies are up to ten times that of Hpd or Photofrin II (P II). They have high quantum yields for inactivation of cells and also relatively low in vivo skin/tumor concentration ratios.

Animals↗
PubMed1988

Hematoporphyrin ethers--II. Improvements in method, synthesis of the dihexyl, dicyclohexanyl and diphenyl ethers and their preliminary biological evaluation.

1. Hematoporphyrin 2.4-dihexyl, -dicyclohexanyl and -diphenyl ethers have been synthesized. 2. Their chemical and physical properties are recorded. The possibility of isomerism is discussed. 3. Preliminary tests have indicated that they possess high photosensitizing efficiency on human cancer cells.

Chromatography, High Pressure Liquid↗
PubMed1988

Photoproducts formed from photofrin II in cells.

Fluorescence and absorption spectra of light-exposed cells containing the tumour-localizing porphyrin preparation Photofrin II (PII) have been studied. Light exposure results in spectral changes that may be due to a photoinduced modification of the porphyrins without breakage of the porphyrin macrocycle and/or to a photoinduced displacement of the porphyrins in the cells. Photochemical reaction involving breakage of the porphyrin macrocycle also occur as can be seen from the loss of absorbance within the Soret band region during light exposure. Singlet oxygen may be involved in the photodegradation of PII in cells since the process is slowed down on bubbling N2 through the samples and is slightly faster in suspensions in Dulbecco's phosphate buffered saline (PBS) made of D2O compared with suspensions in PBS made of H2O. During light exposure a fluorescent product is formed in the cells with fluorescence excitation and emission characteristics similar to those of the "age pigment" lipofuscin (lambda exc = 350 nm, lambda em = 440 nm).

Cell Line↗
PubMed1988

Hematoporphyrin ethers--III. Cellular uptake and photosensitizing properties.

1. The cellular uptake and the efficiency in sensitizing cells to photoinactivation were determined for hematoporphyrin (Hp) diphenyl ether, Hp dicyclohexyl ether and Hp dihexyl ether. 2. The phenyl diether was taken up by the cells to the same degree as was the clinically used porphyrin preparation photofrin II, while the dihexyl and notably the dicyclohexyl ether were taken up 3-4 times better. 3. Furthermore, the quantum yields for photoinactivation of cells were similar for the three diethers and twice as large as that for photofrin II. 4. Fluorescence- and absorption spectroscopy indicate that these findings are related to the fact that photofrin II is much more aggregated in the cells than are the three Hp diethers. 5. When cells loaded with the porphyrins are incubated with porphyrin-free medium containing serum a certain percentage of the cell-bound drug is removed: 14% for photofrin II, 28% for Hp diphenyl ether, 50% for Hp dicyclohexyl ether and 20% for Hp dihexyl ether. 6. With respect to cell uptake and retention of the dyes, the data did not show any uniform relationship to the polarity of the drugs, in contrast to what has been found earlier for Hp diethers of linear hydrocarbons.

Chromatography, High Pressure Liquid↗
PubMed1988

Relationship between changes in antigen expression and protein synthesis in human melanoma cells after hyperthermia and photodynamic treatment.

Hyperthermia and photoactivated hematoporphyrin derivative induce a dose-dependent reduction in the expression of the p250 surface melanoma-associated antigen on the human FME cell line. Expression of this glycoprotein antigen was quantitated by immunofluorescence flow cytometry based on the monoclonal antibody 9.2.27. Decrease in antigen expression was followed by a transient increase above the level for untreated cells, before normalization occurred about one week after treatment. These treatment-induced changes in antigen expression could partly be explained by changes in protein synthesis. This conclusion was based on the following observations: Hyperthermia and photoactivated hematoporphyrin derivative both inhibited protein synthesis. The latter increased again rapidly to rates above normal until antigen expression reached normal level, whereupon the protein synthesis rate decreased to normal. Inhibition of protein synthesis by cycloheximide 1 day after heating, prevented the recovery of antigen expression, demonstrating that protein synthesis is necessary for resumption of normal antigen expression. The changes in both antigen expression and protein synthesis were dose-dependent, and the magnitude and duration of the changes increased with increasing dose. The time courses of the changes in protein synthesis after two different treatments which both inactivated two logs of cells were almost identical, as were the time courses after two lower heat doses inactivating one log of cells. These similarities were reflected in the changes in antigen expression. At the same time as protein synthesis reached its maximum and antigen expression resumed normal level, an increase in the Golgi apparatus was observed ultrastructurally, indicating an increased synthesis rate and transportation of glycoproteins to the cell surface.

Antigens, Neoplasm↗
PubMed1988

Photodynamic effects of Photofrin II on cell division in human NHIK 3025 cells.

Human cervix carcinoma cells of the line NHIK 3025 were exposed to light after 18 h incubation with Photofrin II. After this photodynamic treatment cells in the interphase were retarded with respect to entry into mitosis for a period which increased with increasing light dose. Following the prolonged interphase, an increase in the mitotic index was observed, giving rise to a 3-fold higher level of mitotic cells compared to the control level. Staining of methanol-fixed cells with the DNA-specific dye mithramycin indicated that the increase in mitotic index was due to a prolongation of the metaphase. For all the light doses studied most of the metaphase cells could be characterized as three-group metaphases or c-metaphase-like structures for the first 8 h after treatment. An approximately 10-fold increase above the control level in the number of tripolar mitoses was also observed. A 2h incubation in a Photofrin II-free medium after the 18 h incubation with Photofrin II and before light exposure reduced the fluorescence of the cells by 30 per cent. However, this wash-out period had no effect on the increase in mitotic index after light exposure. A light dose corresponding to 80 per cent survival (as assayed on asynchronous cells) was given to cells in mitosis after Photofrin II incubation. This treatment delayed more than 90 per cent of the metaphase cells from entering the anaphase for at least 1 h. Cells photodynamically treated in the anaphase and telophase entered the interphase at a similar rate as control cells. These observations indicate a temporary block in the initiation of the anaphase and a prolongation of the metaphase. A microscopic study of cells immunologically stained for beta-tubulin 1 h after photodynamic treatment indicated that the organization of the spindle apparatus was disturbed by the photodynamic treatment. Such perturbations are suggested to be the cause of the observed accumulation of cells in mitosis.

Cell Division↗