PHOTOSENSITIZATION BY DRUGS: NALIDIXIC AND OXOLINIC ACIDS

Abstract— The antibacterial drugs, nalidixic acid and oxolinic acid, have been tested as photosensitizers in aqueous solution using 365 nm UV light. Absorption and fluorescence spectra indicate that intramolecular hydrogen bonding stabilizes the unionized form of these compounds in the pH region2–4. The ability of the unionized species to sensitize photooxidation by the type II (singlet oxygen) mechanism was found to be lower than when these drugs were ionized. Comparison withquinoline–3-carboxylic acid and the methyl esters of nalidixic and oxolinic acids emphasised the significance of the hydrogen bonding in relation to the excited state properties. Unionized nalidixic acid undergoes photolysis more readily than the ionized form, apparently by a free radical mechanism, while oxolinic acid is more stable.     

CYTOTOXIC AND MUTAGENIC EFFECTS OF THE PHOTODYNAMIC ACTION OF CHLOROALUMINUM PHTHALOCYANINE AND VISIBLE LIGHT IN L5178Y CELLS

Abstract The cytotoxic and mutagenic effects of chloroaluminum phthalocyanine (CAPC) plus red light have been measured in strains of L5178Y mouse lymphoma cells which differ in their DNA repair capacities. Strain LY-R, deficient in the excision repair of UV-induced dimers, was found to be relatively more sensitive to the cytotoxic effects of CAPC plus light, whereas strain LY-S, deficienl in the repair of DNA double-strand breaks, was more sensitive than strain LY-R to the mutagenic effects of the treatment. Mutation frequencies were measured in LY-S and LY-R sub-strains which were heterozygous or hemizygous at the thymidine kinase (tk) locus. The mutation frequency at the tk locus induced in the heterozygous strain LY-SI by CAPC plus light was lower than that induced by an equitoxic dose of ionizing radiation but similar to that induced by an equitoxic dose of UVC radiation: The mutation frequency at the F., dose of CAPC plus light was approximately 1100 per 10⁶ surviving cells. The induced frequency in strain LY-S1 was much higher than in either tk+l-heterozygous or ik+10 hemizygous strains of LY-R. The rate and extent of incorporation of CAPC by the LY-R strains was somewhat greater than for strain LY-S1 at early times after CAPC addition, but by the time the cells were irradiated (18 h after CAPC addition) the difference was not great enough to account for the difference in cytotoxicity. It is possible that the cytotoxic and mutagenic lesions differ and that either the quantities of the respective lesions induced or the efficiencies of repair of the respective lesions differ inversely in the two strains. light have been measured in strains of L5178Y mouse lymphoma cells which differ in their DNA repair capacities. Strain LY-R, deficient in the excision repair of UV-induced dimers, was found to be relatively more sensitive to the cytotoxic effects of CAPC plus light, whereas strain LY-S, deficienl in the repair of DNA double-strand breaks, was more sensitive than strain LY-R to the mutagenic effects of the treatment. Mutation frequencies were measured in LY-S and LY-R sub-strains which were heterozygous or hemizygous at the thymidine kinase (tk) locus. The mutation frequency at the tk locus induced in the heterozygous strain LY-SI by CAPC plus light was lower than that induced by an equitoxic dose of ionizing radiation but similar to that induced by an equitoxic dose of UVC radiation: The mutation frequency at the F., dose of CAPC plus light was approximately 1100 per 10⁶ surviving cells. The induced frequency in strain LY-S1 was much higher than in either tk+l-heterozygous or ik+10 hemizygous strains of LY-R. The rate and extent of incorporation of CAPC by the LY-R strains was somewhat greater than for strain LY-S1 at early times after CAPC addition, but by the time the cells were irradiated (18 h after CAPC addition) the difference was not great enough to account for the difference in cytotoxicity. It is possible that the cytotoxic and mutagenic lesions differ and that either the quantities of the respective lesions induced or the efficiencies of repair of the respective lesions differ inversely in the two strains.     

FISHERY BENEFITS OF FULLY PROTECTED MARINE RESERVES: WHY HABITAT AND BEHAVIOR ARE IMPORTANT

ABSTRACT. Fully protected marine reserves, areas that are closed to all fishing, have attracted great interest for their potential to benefit fisheries. A wide range of models suggest reserves will be most effective for species that are relatively sedentary as adults but produce offspring that disperse widely. Adult spawning stocks will be secure from capture in reserves, while their offspring disperse freely into fishing grounds. Such species include animals like reef fish, mollusks and echino‐derms, and models typically indicate that when they are over‐fished, catches will be higher with reserves than without. By contrast, the same models suggest that reserves will be ineffective for animals that are mobile as adults species like cod, tuna or sharks. They remain vulnerable to fishing whenever they move outside reserves. Unfortunately, most models lack sufficient realism to effectively gauge reserve effects on migratory species. They usually assume that individuals are homogeneously distributed in a uniform sea and move randomly. They also assume that fishers hunt at random. Neither is true. For centuries, fishers have targeted places and times when their quarry are most vulnerable to capture. Protecting these sites could have disproportionately large effects on stocks. Furthermore, models rarely take into account possible benefits from improvements in habitat within reserves. Such changes, like increased biomass and complexity of bottom‐living organisms, could alter fish movement patterns and reduce natural mortality rates in ways that enhance reserve benefits. We present a simple model of reserve effects on a migratory fish species. The model incorporates spatial variation in vulnerability to capture and shows that strategically placed reserves can offer benefits in the form of increased spawning stock and catch, especially when fishing intensities are high. We need to develop a new generation of models that incorporate habitat and behaviour to better explore the utility of reserves for mobile species. Migratory behavior does not preclude reserves from benefiting a species, but it demands that we apply different principles in designing them. We must identify critical sites to species and develop reserve networks that focus protection on those places.     

An Algorithm for Least-Squares Circle Fitting to Data with Specified Uncertainty Ellipses

The problem considered here is that of fitting a circle to aset of measured data points specified in terms of their cartesiancoordinates. It is assumed that the data adequately representsa circle and that associated with each data point there is anuncertainty ellipse describing the measurement error. A weightednonlinear least-squares problem is formulated in order to determineunbiased estimates of the centre and radius of the circle whichbests fits the given data. The resulting problem displays structurewhich is exploited when the Gauss-Newton algorithm is used toobtain a solution. In addition to estimates of the circle parametersthe algorithm produces error ellipses for the centre of thecircle and any point on its circumference.     

ENHANCED GROWTH AND EXPERIMENTAL METASTASIS OF CHEMICALLY INDUCED TUMOR IN ULTRAVIOLET IRRADIATED SYNGENEIC MICE

Abstract— Recent studies have shown that ultraviolet (UV) irradiation induces a systemic effect which enhances subsequent tumor induction by benzo[a]pyrene in a manner which is dependent on the dose of benzo[a]pyrene. The present study was designed to test whether UV-B irradiation renders mice susceptible to subcutaneous or intravenous injection of a regressor tumor induced by benzo[a]pyrene. The sources of UV-B irradiation were banks of 6 Westinghouse FS-40 sunlamps, situated 20 cm above the mouse cages. Female BALB/cAnNHsd received five 30-min dorsal UV-B radiation treatments per week for 12 weeks, resulting in a total dose of approx. 6.4 × 10⁵ J m^-2. Two to seven days after termination of UV treatments, syngeneic regressor tumor cells (BP2) induced by benzo[a]pyrene were injected subcutaneously or intravenously into irradiated mice and unirradiated controls. By 38 days post subcutaneous implantation, 24/30 and 3/30 BP2 implants were detectable in the irradiated and unirradiated mice, respectively. Ultraviolet irradiated mice were also unable to reject lung colonies resulting from intravenous administration of BP2 cells, although they were rejected by unirradiated mice. The mean number of lung colonies per mouse was 16- to 35-fold greater in UV irradiated mice than in unirradiated controls, at 14 to 17 days post injection. Thus, UV irradiation rendered mice, with no known exposure to benzo[a]pyrene, susceptible to a subcutaneous or intravenous injection of a regressor tumor induced by benzo[a]pyrene.