718 RADIATION BIOLOGY 



the lines indicated in Blum's three postulates, together with a recognition 

 of the differences between sensitivity to light and photodynamic action. 



ADDENDUM 



Since this chapter was completed, several papers dealing with the 

 mechanism of photodynamic action have reached the writer. In vitro 

 experiments (Galston, 1950; Weil and Buchert, 1951) indicate that histi- 

 dine, tryptophan, and tyrosine are the groups in proteins most susceptible 

 to photosensitized oxidation, whereas cystine and methionine are little 

 affected. However, Calcutt (1951) suggested that irradiation makes 

 sulfhydryl groups more vulnerable to oxidation and attributed to this the 

 hastening of the photosensitized killing of paramecia that had been 

 irradiated before addition of the photosensitizer. 



Galston (1950) has shown that the growth of sections of etiolated pea 

 epicotyl is inhibited by light in the presence of riboflavin through photo- 

 sensitized oxidation of indoleacetic acid, and that in the plant itself a 

 similar action occurs with a flavoproteih as the sensitizer. In the mecha- 

 nism postulated for this reaction, the light-activated riboflavin acts as a 

 hydrogen carrier between the indoleacetic acid and oxygen. Weil and 

 Maher (1950) propose a similar mechanism for photosensitized oxidation 

 of nicotine by methylene blue, and since they detected hydrogen peroxide 

 during the course of the reaction, Weil and Maher attribute the final 

 stage to oxidation by peroxide. Furthermore the role of the light- 

 activated flavoprotein enzyme of Galston is the production of hydrogen 

 peroxide, which through a peroxidase oxidizes indoleacetic acid. The 

 photodynamic aspects of these reactions may be expressed in the follow- 

 ing terms: 



D + hv-^D', (15-1) 



D' + H2X -> X + Z)H2, (15-2) 



DH, + 02-^ H2O2 + D. (15-3) 



Here D is the sensitizer, and H2X is a hydrogen-donor substrate. Thus, 

 in the system studied by Galston, D is the flavoprotein, H2X is indole- 

 acetic acid, and the final stage (not shown in the equations) is the oxi- 

 dation of the indoleacetic acid by peroxide-peroxidase ; in that of Weil 

 and Maher, H2A" is nicotine, D is methylene blue, and in the final reaction 

 the product X of Eq. (15-2) undergoes further oxidation by peroxide. 

 In both systems carbon dioxide is an end product of the series of reactions. 

 The mechanisms suggested in these reactions emphasize the possibility 

 that photodynamic action may proceed by various paths according to 

 the circumstances. There is a need for critical study of these various 

 mechanisms using sensitizers of various classes and with measurement of 

 oxygen consumption, substrate disappearance, and ideally of the nature 



