THE MECHANISM OF ACTION OF METHYL 

 XANTHINES IN MUTAGENESIS 



Arthur L. Koch 



Department of Biochemistry, College of Medicine, J. Hillis Miller 

 Health Center, University of Florida, Gainesville, Florida 



Abstract — The biochemical findings relating to the action of methyl xanthines on bacteria 

 and bacterial extracts have been reviewed. These observations, together with those of Novick 

 and SziLARD on the mutagenic activity of these substances, have suggested that the biological 

 action results from an inhibition of enzymes of nucleic acid biosynthesis. Consequences of 

 this hypothesis have been discussed relative to the regulation of growth of cell constituents. 

 Alternative hypotheses are enumerated. 



I. INTRODUCTION 



A NUMBER of agents, both chemical substances and radiations, cause mutations. 

 One particular class appears to be potentially most fruitful in an attempt 

 to understand the genetic replication process. This class includes purines and 

 related compounds. Particularly important are the plant alkaloids responsible 

 for the pharmacological effects of coffee, tea and cocoa. If these substances 

 are added to a continuously growing culture of bacteria, the mutation rate 

 is caused to increase markedly (1, 2). 



If we compare the structures (Fig. 1) of the alkaloids caffeine, theobromine 

 and theophylline, with the purine bases normally present in nucleic acids of 



Me N- 



= C C- 



,/ 



Me 



Me N C- 



CAFFEINE 



H N- 



Me N- 



Me 



> 



THEOBROMINE 



Me N C-= 



I I 



SI 



Me- 



-N C- 



THEOPHYLLINE 





XANTHINE 



-NH, 





-OH 



H2N C 



/ 



ADENINE 



Fig. 1 . The structure of purine derivatives 



GUANINE 



all species, adenine and guanine, the similarity is readily apparent. The former 

 are methyl derivatives of xanthine, the latter amino and deoxy derivatives of 

 xanthine. It is tacitly assumed that these agents are mutagens because of this 

 similarity. 



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