Physico-Chemical Evaluation of Rationally Designed Melanins as Novel Nature-Inspired Radioprotectors (original) (raw)
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Ability of Melanins to Protect Against the Radiolysis of Thymine and Thymidine
Pigment Cell Research, 1987
Individuals with black skin rarely get skin cancer, and melanomas, tumors arising from pigmented cells, are generally resistant to radiation therapy. The role of melanin in these two phenomena has not been defined, but oxygen-radical species have been implicated in both effects. These studies were undertaken to determine the ability of various melanins to compete for ionizing radiation-produced radicals which destroy nucleic acid bases. The ability of Sigma eumelanin (S-eumelanin) to protect against the radiolysis of thymidine in buffered solutions was compared to the protective ability of seven amino acids, including melanin precursors; bovine serum albumin, as a model protein; ficoll, as a model polysaccharide; and DNA. Both proteins and polysaccharides are known to scavenge hydroxyl radicals in cells. The concentration of thymidine after exposure to gamma radiation was determined by High Performance Liquid Chromatography (HPLC) analysis after removal of insoluble melanin by acid precipitation. Seumelanin was more effective at competing with thymidine for free radicals than bovine serum albumin, Ficoll, or DNA, but less effective than certain of the small molecules. Several of the above compounds were also examined for ability to protect against thymine radiolysis. In addition, melanins from other sources were compared to Seumelanin. Of these, enzymatically synthesized phaeomelanin was the most effective.
Pigment Cell & Melanoma Research, 2007
Melanized microorganisms are often found in environments with very high background radiation levels such as in nuclear reactor cooling pools and the destroyed reactor in Chernobyl. These findings and the laboratory observations of the resistance of melanized fungi to ionizing radiation suggest a role for this pigment in radioprotection. We hypothesized that the radioprotective properties of melanin in microorganisms result from a combination of physical shielding and quenching of cytotoxic free radicals. We have investigated the radioprotective properties of melanin by subjecting the human pathogenic fungi Cryptococcus neoformans and Histoplasma capsulatum in their melanized and non-melanized forms to sublethal and lethal doses of radiation of up to 8 kGy. The contribution of chemical composition, free radical presence, spatial arrangement, and Compton scattering to the radioprotective properties of melanin was investigated by high-performance liquid chromatography, electron spin resonance, transmission electron microscopy, and autoradiographic techniques. Melanin protected fungi against ionizing radiation and its radioprotective properties were a function of its chemical composition, free radical quenching, and spherical spatial arrangement.
Pigment Cell Melanoma Research, 2007
Melanized microorganisms are often found in environments with very high background radiation levels such as in nuclear reactor cooling pools and the destroyed reactor in Chernobyl. These findings and the laboratory observations of the resistance of melanized fungi to ionizing radiation suggest a role for this pigment in radioprotection. We hypothesized that the radioprotective properties of melanin in microorganisms result from a combination of physical shielding and quenching of cytotoxic free radicals. We have investigated the radioprotective properties of melanin by subjecting the human pathogenic fungi Cryptococcus neoformans and Histoplasma capsulatum in their melanized and non-melanized forms to sublethal and lethal doses of radiation of up to 8 kGy. The contribution of chemical composition, free radical presence, spatial arrangement, and Compton scattering to the radioprotective properties of melanin was investigated by high-performance liquid chromatography, electron spin resonance, transmission electron microscopy, and autoradiographic techniques. Melanin protected fungi against ionizing radiation and its radioprotective properties were a function of its chemical composition, free radical quenching, and spherical spatial arrangement.
Photochemistry and Photobiology, 1984
Rose Bengal is shown to photosensitize free-radical production and oxygen consumption in solutions of melanin from autooxidation of 3,4-dihydroxyphenylalanine (DOPA). In anaerobic solutions the sensitizer enhances rates of free-radical production by up to a factor of 20. In aGrobic solutions, rates of oxygen consumption can be increased by a factor of several hundred. The reactions appear to involve the triplet state of the sensitizer. The effect of the sensitizer in increasing oxygen consumption is quenched by low concentrations of azide and enhanced by DZO, suggesting that a singlet oxygen mechanism is involved.
PLoS ONE, 2007
Background. Melanin pigments are ubiquitous in nature. Melanized microorganisms are often the dominating species in certain extreme environments, such as soils contaminated with radionuclides, suggesting that the presence of melanin is beneficial in their life cycle. We hypothesized that ionizing radiation could change the electronic properties of melanin and might enhance the growth of melanized microorganisms. Methodology/Principal Findings. Ionizing irradiation changed the electron spin resonance (ESR) signal of melanin, consistent with changes in electronic structure. Irradiated melanin manifested a 4-fold increase in its capacity to reduce NADH relative to non-irradiated melanin. HPLC analysis of melanin from fungi grown on different substrates revealed chemical complexity, dependence of melanin composition on the growth substrate and possible influence of melanin composition on its interaction with ionizing radiation. XTT/MTT assays showed increased metabolic activity of melanized C. neoformans cells relative to non-melanized cells, and exposure to ionizing radiation enhanced the electron-transfer properties of melanin in melanized cells. Melanized Wangiella dermatitidis and Cryptococcus neoformans cells exposed to ionizing radiation approximately 500 times higher than background grew significantly faster as indicated by higher CFUs, more dry weight biomass and 3-fold greater incorporation of 14 C-acetate than non-irradiated melanized cells or irradiated albino mutants. In addition, radiation enhanced the growth of melanized Cladosporium sphaerospermum cells under limited nutrients conditions. Conclusions/Significance. Exposure of melanin to ionizing radiation, and possibly other forms of electromagnetic radiation, changes its electronic properties. Melanized fungal cells manifested increased growth relative to non-melanized cells after exposure to ionizing radiation, raising intriguing questions about a potential role for melanin in energy capture and utilization.
A biomimetic approach to shielding from ionizing radiation: The case of melanized fungi
PLOS ONE, 2020
Melanized fungi have been shown to thrive in environments with high radionuclide concentrations, which led to the association of the pigment melanin with the protection against ionizing radiation. Several hypotheses regarding the function of melanin have been proposed. Yet, the exact mechanism behind the protective property of melanin is unclear and poorly explored. A better understanding of the mechanisms that are involved in increasing the tolerance of the organisms to ionizing radiation could lead to technology transfer to humanrelated applications. Effective protection from radiation is essential for human space flight in general and human missions beyond Low Earth Orbit specifically. In this paper, we follow a biomimetic approach: we test two of current hypotheses and discuss how they could be applied to radiation shield designs. First we focus on the interaction of melanin with high energy electrons, which has been suspected to reduce the kinetic energy of the electrons through a cascade of collisions, thus providing physical shielding. Second, we investigate if the spatial arrangement of melanin, organized as a thin film or a collection of hollow microspheres, affects its shielding properties. To this end, we measured experimentally and by numerical simulations the attenuation of β-radiation as pass through solutions and suspensions of melanin and contrasted the values to the ones of cellulose, a substance with similar elemental composition. Further, we investigate the spatial arrangement hypothesis using Monte Carlo simulations. In agreement with the simulations, our experiments indicated that melanin does not provide improved shielding in comparison to cellulose from β-radiation. However, our simulations suggest a substantial effect of the spatial arrangement on the shielding performance of melanin, a pathway that could be transferred to the design of composite radiation shields.
Biochimica et Biophysica Acta (BBA) - General Subjects, 1985
A pu!se radiolysis investigation of the oxidation of the melanin precursors 3,4-dihydroxyphenylalanine (dopa) and the cysteinyldopas The unstable quinones of 3,4-dihydroxyphenylalanine (dopa) and the most abundant cysteinyldopa isomers (2S-, 5S-and 2,5S,S'-) have been generated rapidly via disproportionation of their respective semiquinones prepared pulse radiolytically by one-electron oxidation of the corresponding dopes with azide radicals. Dopaquinone decays via a base-catalysed unimolecular cyclisation yielding leucodopachrome which, under the present conditions, is immediately oxidised by remaining dopaquinone to form dopachrome and dopa back again. Addition of cysteine increased the rate of dopaquinone decay and precluded dopachrome formation. By contrast, the cysteinyldopa quinones decayed via an acid-catalysed unimolecular cyclisation involving the cysteine side chain to form a cyclic quinone-imine observed directly for the first time. These quinone-imine intermediates subsequently rearranged to more stable phenolic benzothiazine isomers. The addition of cysteine had little effect on cysteinyldopa quinone decay and did not prevent quinone-imine formation. The absorption spectra, extinction coefficients and rate constants for formation and decay of these various transient species involved in melanisation are reported. 0304-4165/85/$03.30
Photoelectrochemical properties of melanin
Nature Precedings, 2007
Melanin is to the animal kingdom like chlorophyll to the vegetal kingdom(1). Melanin collects energy from lower-energy radiation sources, kicks electrons into excited states, initiating a process that would end up producing chemical energy, similar to the way in which photosynthesis supplies energy to plants. However, the precise roles of melanin during this process are unknown. Here we show that the increase in the electron-transfer properties of melanin is independent of the energy of the incident photons. We found in controlled in vivo assays that melanin has the remarkable capability of converting lower-energy radiation towards a more useful form of energy. Furthermore, we found that melanin can break up water molecules and giving up energy suggesting an additional behavior mode for melanin. Our results demonstrate how members of the melanin family are likely to function as transducers, oxidizing water, pushing apart water molecules, as well as recruiting back ions into molecule...