Phthalocyanines as photosensitizers in biological systems and for the photodynamic therapy of tumors.
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Biomedical subjects
Publications and source records attributed to J D Spikes.
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The preliminary studies reported here show that at least some lipid soluble porphyrins can easily be incorporated into the membranes of liposomes prepared with different phospholipids; such porphyrins do not leach out of the membranes when the liposomes are stored in aqueous media. In this environment, the lipid soluble porphyrins are very effective photodynamic sensitizers for lipophilic substrates in the liposome membrane, for external amino acids and proteins, and for mammalian cells.
Sheep liver beta-N-acetylhexosaminidase was purified over 20-fold by conventional methods. The enzyme possessed activity against both p-nitrophenly-beta-D-N-acetylglucosaminide and p-nitrophenyl-beta-D-N-acetylgalactosaminide as substrates. On the basis of a variety of physical and chemical analyses including pH stability, substrate inhibition studies and photodynamic inactivation, it was concluded that both the beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase activities reside within the same molecule.
Recommendations for future research on photocarcinogenesis were developed during an international conference on UVR carcinogenesis. Areas covered in the recommendations include research at the molecular biology level, human (especially epidemiologic aspects), physical (including instrumentation), and biologic studies (stressing animal models). The recommendations also propose the establishment of central supply and service sources for photocarcinogenesis research as well as the establishment of interdiscipilinary training programs related to research in photocarcinogenesis.
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The time course of skin tumor induction was determined in hair-clipped inbred agouti C3Hf mice irradiated three times per week with a medium-pressure quartz-mercury lamp; 4 different UV doses were used. Although the ears were also exposed to the radiation, in the 3 groups given the highest doses no ear tumors were observed by the time each animal had developed at least 1 tumor on its back. No tumors were found in the animals receiving the lowest UV dose. In the group receiving the highest dose, males developed tumors earlier than did females; this trend continued in the lower dose groups. Many tumors that developed in the back skin were well-differentiated squamous cell carcinomas. Others were less well-differentiated squamous cell carcinomas. Others were less well defined so that the cell of origin was difficult to determine. In the group receiving the highest UV dose, the squamous cell carcinomas were few, whereas at the lower doses they predominated.
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A large series of compounds was screened for ability to protect trypsin from eosin-sensitized photodynamic inactivation. Eosin-sensitized photooxidation reactions of this type typically proceed via the triplet state of the dye and often involve singlet state oxygen as the oxidizing entity. In order to determine the mechanisms by which trypsin is protected from photoinactivation, a number of good protective agents (inhibitors) and some non-protective agents were selected for more detailed flash photolysis studies. Good inhibitors such as p-phenylenediamine, n-propyl gallate, serotonin creatinine sulfate and p-toluenediamine competed efficiently with oxygen and with trypsin for reaction with the triplet state of eosin. The inhibitors were shown to quench triplet eosin to the ground state and/or reduce triplet eosin to form the semireduced eosin radical and an oxidized form of the inhibitor. In the latter case, oxidized inhibitor could react by a reverse electron transfer reaction with the semi-reduced eosin radical to regenerate ground state eosin and the inhibitor. The good inhibitors also competed effectively with trypsin for oxidation by semioxidized eosin, thus giving another possible protective mechanism. Non-inhibitors such as halogen ions and the paramagnetic ions Co++, Cu++ and Mn++ reacted only slowly with triplet and with seimioxidized eosin. The primary pathway for the eosin-sensitized photooxidation of trypsin at pH 8.0 involved singlet oxygen, although semioxidized eosin may also participate.
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