PHOTODYNAMIC ACTION 703 



some of the sporadic photosensitivity associated with plants such as 

 legumes and rape may be caused by such a pigment. However, this 

 pigment has not been detected in green leaves of P. miliaceum, and 

 lambs dosed with preparations of the pigments in amounts much greater 

 than they could obtain by eating the dried plant were not photosensitive. 



It has also been found that rats can be photosensitized by a chlorophyll 

 derivative present in sheep feces. 



Such observations point to the dangers inherent in the use of rats and 

 guinea pigs as experimental animals in testing for photosensitizing sub- 

 stances in plants or extracts of plants. The discovery of these pigments 

 in P. miliaceum actually arose during feeding tests of plant extracts for 

 a substance producing liver dysfunction, accompanied by phylloerythrin 

 photosensitivity, in sheep and guinea pigs, so that the production of 

 photosensitivity by the pigment present in these extracts proved quite 

 misleading. 



NATURE OF THE SUBSTRATE IX PHOTODYNAMIC ACTION 



The identity of the substrate that undergoes oxidation — the molecule 

 represented by X in Schemes I and II — has not been definitely deter- 

 mined. The substrate is either a substance essential for normal struc- 

 ture or metabolism of the cell or a substance that on oxidation gives rise 

 to a toxic product, and since a wide variety of types of cells are affected, 

 it apparently occurs universally in living matter. Most of the evidence 

 available indicates that this substance is a protein constituent. The 

 uptake of oxygen by photosensitized tissue extracts (Kosman and Lillie, 

 1935) or blood plasma (Smetana, 1938) appears to be determined by 

 the protein rather than by the lipin fraction present in these systems. 

 Smetana found that the action of light on a protein in the presence of a 

 photosensitizer can completely destroy the antigenicity of the protein. 

 Harris (1926) has shown that proteins, including albumins and hemo- 

 globin, and the amino acids tyrosine and tryptophan undergo photo- 

 oxidation in ultraviolet light and that this oxidation is accelerated by 

 the presence of hematoporphyrin and other fluorescent substances. Of 

 particular interest was his demonstration that gelatin, which does not 

 contain tyrosine and tryptophan, was not affected by photodynamic 

 action. Unfortunately the experiments of Harris do not clearly distin- 

 guish between effects of ultraviolet light and photodynamic action. 

 Carter (1928) concluded that the presence of easily oxidizable groupings, 

 such as those in oleic acid and acetaldehyde, was not itself sufficient to 

 ensure photodynamic oxidation and that aliphatic compounds were not 

 affected. The structure common to susceptible compounds appeared to 

 be hydroxyl or amino groups attached to a benzene ring. Among amino 

 acids, Carter and also Lieben (1927) recorded uptake of oxygen by 

 histidine as well as by tyrosine and tryptophan. 



