Chapter VI 



INTRODUCTION 



The mast cell and carcinogenesis 



MY own introduction to the mast cell occurred during student days, 

 fortunately, perhaps, before the relationship of the mast cell to 

 heparin had been discovered. One of my teachers in Edinburgh, 

 the late Mr. J. J. M. Shaw, remarked that, in the course of some experiments on 

 tar cancer in mice, he had confirmed an earlier observation of an increase in 

 the mast-cell content of the painted skin (cf. Woglom, 1926). On being asked 

 what was the function of these numerous cells with blue or purple granules, 

 Mr. Shaw replied that he did not know. This confession of ignorance on the 

 part of a favourite teacher was in itself so stimulating that I never forgot the 

 mast cells : in particular, the thought remained that in some way the mast cell 

 might provide a clue to the mechanism of carcinogenesis. 



A few years later the first pure carcinogenic hydrocarbon, 1, 2, 5, 6- 

 dibenzanthracene, was identified and synthesized. This and other carcinogenic 

 hydrocarbons dissolved in a non-irritant solvent, acetone, were used to paint 

 the skin of a group of mice and were found to elicit a mast-cell reaction in the 

 dermis similar to that which followed application of crude coal tar dissolved 

 in benzene. When commercial heparin became available an attempt was made 

 to influence the course of carcinogenesis by injecting heparin under the painted 

 skin. Unfortunately, no clear cut results emerged from these latter experiments, 

 nor from a more extensive investigation on the effects of injecting or feeding 

 tumour-bearing mice with dyes which combine with heparin in vitro (Riley, 

 1948). Despite the disappointments, these early experiments at least confirmed 

 my interest in the mast cells and raised the suspicion that these cells probably 

 had functions other than the elaboration of an active anticoagulant for the 

 blood. 



Shortly after the war I came across the interesting monograph by Sylven 

 (1941) who stated that the mast cells release a metachromatically-staining 

 k free chromotrope substance' (F.C.S.) into the connective tissues during wound 

 repair: and since Fell and Danielli (1943) had found a comparable increase of 

 the enzyme alkaline phosphatase during fibroplasia, Dr. J. M. Drennan and I 

 (1949) examined the distribution of mast cells, F.C.S. and alkaline phosphatase 

 in a wide variety of animal tissues in the hope of finding a functional relation- 

 ship. Again there was disappointment, but we did notice that in certain species 

 the mast cells appeared to be migrating and maturing in a direction away from 

 their origin around small blood vessels. This led my own thinking back to 



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