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Biomedical subjects

J Moan

Publications and source records attributed to J Moan.

At least 199 records · Page 11Linked to original sources
PubMed1981

Photodynamic effects on human cells exposed to light in the presence of hematoporphyrin. Localization of the active dye.

Human cells of the line NHIK 3025 were exposed to light in the presence of hematoporphyrin. Cellular inactivation, induction of single-strand breaks in the DNA and cellular uptake of hematoporphyrin were measured under different conditions. It was concluded that hematoporphyrin bound to or taken up by the cells leads to photoinactivation and photoinduction of single-strand breaks in the DAN, while hematoporphyrin present in the medium outside the cells is of no significant importance.

Cell Line↗
PubMed1981

Uptake of hematoporphyrin derivative and sensitized photoinactivation of C3H cells with different oncogenic potential.

Four types of mouse embryo fibroblast cells of different oncogenic potential were investigated with respect to uptake of the tumor localizing agent hematoporphyrin derivative (Hpd) and sensitized photoinactivation. Cell size and cellular content of Hpd were measured simultaneously for single cells by means of flow cytofluorimetry. The more malignant cell types had a slightly higher porphyrin uptake per unit cellular volume than the untransformed type, while the photosensitivity of cells incubated with Hpd was equal for all the cell types. Since Hpd seems to concentrate in membranes, this may be related to the fact that the membrane areas of malignant cells are relatively larger than that of untransformed cells, due to the presence of more microvilli. The present study indicates that the preferential localization of Hpd in tumors, as well as the high efficiency of phototherapy reported in the literature, are due to extracellular differences between the tumors and normal tissue.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Photodynamic effects of haematoporphyrin derivative on synchronized and asynchronous cells of different origin.

Phototherapy in the presence of haematoporphyrin derivative has been shown to have a preferential effect on malignant tumours when compared to normal tissue. This communication presents a comparison of the sensitivity to photochemotherapy in vitro of different cell lines. Asynchronous populations of cells were exposed to light in the presence of haematoporphyrin derivative, and found to be inactivated with a comparable efficiency. The lines were of human, Chinese-hamster or mouse origin and had different abilities to form tumours after heterotransplantation into nude mice or transplantation into syngeneic, immunosuppressed mice. Synchronized cells from 4 of the lines showed a similar variation in sensitivity to light throughout the cell cycle. Cells near the middle of interphase showed the highest sensitivity, whilst cells in early G1 were found to be least sensitive towards treatment with haematoporphyrin derivative and light.

Animals↗
PubMed1980

Photodynamic effects on human cells exposed to light in the presence of hematoporphyrin. pH effects.

Human cells derived from a carcinoma in situ (NHIK 3025) were exposed in vitro to visible light and hematoporphyrin at different pH levels. The cells were inactivated more efficiently at pH 6.7 and 7.2 than at pH 7.8 The treatment with light and hematoporphyrin also induced DNA damage more efficiently at the former pH values than at the latter one. The variation in the efficiency of the photodynamic effect with the pH is mainly due to the fact that the cellular uptake of hematoporphyrin increases with decreasing pH.

Chromosome Aberrations↗
PubMed1980

Binding of hematoporphyrin to synchronized cells from the line NHIK 3025.

The binding of hematoporphyrin (HP) to human cells of the line NHIK 3025 has been studied with the aid of microfluorometry. HP is concentrated within cells when present in Hank's balanced salt solution in the concentration range 10(-5)--3 x 10(-3) M. The time course of binding is biphasic with a rapid initial binding and a slower accumulation at times longer than 30 min. The amount bound to HP increases linearly as the cells proceed through the cell cycle and is doubled from early G1 to late G2.

Carcinoma in Situ↗
PubMed1980

DNA single-strand breaks and sister chromatid exchanges induced by treatment with hematoporphyrin and light or by x-rays in human NHIK 3025 cells.

Alkali-labile sites resulting in single-stranded breaks in DNA and sister chromatid exchanges are produced when human cells (NHIK 3025) in vitro are exposed to sublethal doses of light in the presence of hematoporphyrin. The irradiation doses required to reduce the survival from 1 to 0.1 for 220-kV X-rays and treatment with 10(-4) M hematoporphyrin in phosphate-buffered saline and 380 nm light were 6.2 grays and 230 J/sqm, respectively. X-rays induce about 5 times more sister chromatid exchanges and about 80% more DNA single-strand breaks than exposure to hematoporphyrin plus light when the two modalities of treatment are compared on the same level of survival. In both cases, the single-strand breaks are practically completely repaired within 15 min.

Cell Line↗
PubMed1979

Detection of singlet oxygen production by ESR.

SINGLET molecular oxygen is a very powerful oxidant. Its action is important in a variety of chemical and biological processes(1-4), for examples dye-sensitised photooxidation of lipids, proteins and nucleic acids(4), photodynamic inactivation of viruses(5) and cells(4), phototherapy of cancer(6,7), carcinogenesis(8), haemolysis of erythocytes(9), sensitisation of the human skin(4) and degradation of food(4). The methods used to detect singlet oxygen are unspecific, of low sensitivity or laborious. Photooxidation of 1,3-diphenylisobenzofuran seems to be the most widely used diagnostic test for (1)O(2). However, in the absence of additional control experiments this test does not prove the intermediacy of (1)O(2) (ref. 4) and 1,3-diphenylisobenzofuran has very low solubility and dimerises in aqueous solutions. Lion et al.(10) have proposed a new method to detect (1)O(2) involving the generation of stable nitroxide radicals when (1)O(2) reacts with the sterically hindered amine 2,2,6,6,-tetramethylpiperidin. When using this method to detect (1)O(2) in neutral aqueous solutions, we found no radical production. We report here our investigation of this problem, as it is biologically important to be able to detect (1)O(2) production in such solutions.

Journal Article↗
PubMed1979

Photodynamic inactivation of cancer cells in vitro. Effect of irradiation temperature and dose fractionation.

Human cancer cells in vitro (NHIK 3025), derived from a carcinoma in situ are inactivated when exposed to visible light in the presence of hematoporphyrin. Irradiation at 4 degrees C results in much more efficient inactivation than irradiation at 37 degrees C. Furthermore, a given total light dose is more efficient when it is fractionated than when it is given in a single exposire. These findings may be taken advantage of in future photochemotherapy of cancer.

Cell Division↗
PubMed1979

The mechanism of photodynamic inactivation of human cells in vitro in the presence of haematoporphyrin.

The photosensitizing effect of haematoporphyrin (HP) on human cells of the established line NHIK 3025 has been studied. Fluorescence measurements show that HP is bound to these cells. Serum proteins also bind HP, and the presence of 10% human serum during incubation with HP (3 X 10(-4)M) reduces the cellular uptake of HP by 75% or more. The photosensitized inactivation is enhanced when the cells are suspended in D2O-buffer during irradiation. This indicates that singlet oxygen is involved in the inactivation. Two findings indicate that the photoinduced damage is repairable: firstly, the fraction of cells surviving a given light dose decreases with decreasing irradiation temperature, and secondly, the survival curves have a shoulder at low exposures of light.

Cell Line↗
PubMed1979

Photodynamic effect of haematoporphyrin throughout the cell cycle of the human cell line NHIK 3025 cultivated in vitro.

Cells from the established cell line NHIK 3025 were synchronized by repeated mitotic selections. Survival of the synchronized cells after treatment with haematoporphyrin and near-UV light was measured by testing the capacity of the cells to form macroscopic colonies. The sensitivity to photodynamic inactivation was small in early G1, late S and G2. The sensitivity increased throughout late G1 and early S to a maximum in mid S. More than a 100-fold variation is found in the survival after 20 min irradiation in the presence of 4 X 10(-4)M haematoporphyrin.

Cell Cycle↗
PubMed1979

Photodynamic inactivation of synchronized human cells in vitro in the presence of hematoporphyrin.

Dose-response curves for inactivation of synchronized cells from the human cell line NHK 3025 in the presence of hematoporphyrin and light are shown. Sensitivity toward photodynamic inactivation is increasing as the cells move in the cell cycle from G1 to mid-S. The increase is mostly due to a change in the extent of the shoulder of the dose-response curve at low doses. The quasithreshold dose (Dq) is high in early G1 and much lower in mid-S. No great variations were found in the slope (1/Do) of the dose-response curves at high doses. The shape of the dose-response curves indicates a higher capacity for repair of sublethal damage in the early part of the cell cycle than in the later stages.

Cell Cycle↗
PubMedDate not supplied

No correlation between DNA strand breaks and HPRT mutation induced by photochemical treatment in V79 cells.

DNA strand breaks, measured by alkaline elution, and hypoxanthine guanine phosphoribosyltransferase (HPRT) mutation were studied in V79 cells after photochemical treatment (PCT) or exposure to X-rays. Cells were incubated with the photosensitizers Photofrin II (PII) and three closely related porphyrins tetra-(3-hydroxyphenyl) porphyrin (3THPP), meso-tetra-(4-sulfonatophenyl) porphine (TPPS4) and meso-tetra-(N-methyl-4-pyridyl) porphine (TMPyPH2). These dyes are assumed to act on cellular targets mainly via singlet oxygen when excited by light. While the hydrophilic TPPS4 and TMPyPH2 did not photoinduce mutants to any significant extent, both lipophilic dyes, 3THPP and PII, were significantly mutagenic when excited by light. On the other hand, TPPS4 was the most efficient sensitizer of alkali-labile DNA strand breaks, while TMPyPH2 did not induce any significant amount of either type of DNA damage. Surprisingly, no correlation between the two parameters was found for PCT, either after exposures inactivating 50% of the cells or after exposures inactivating 90% of them. The lack of correlation between the yields of DNA strand breaks and of mutants could not be explained by differences in the intracellular localization pattern of the dyes.

Animals↗