MAST CELLS AND HISTAMINE IN SKIN 



showed me a paraffin section of precancerous mouse skin which he had stained 

 with eosin-toluidine blue. This simple alternative method of staining had 

 immediately revealed a dense collection of dermal mast cells, not one of which 

 could be recognized in a corresponding section stained by the routine 

 haematoxylin-eosin method. However, it was only when I heard that nothing 

 was then known of the mast cell's function that my curiosity was sufficiently 

 stimulated to make me pause and read any subsequent reference to mast cells 

 in the medical literature. 



In 1938 I noticed an abstract of the paper by Holmgren and Wilander (1937) 

 on the combined histological and biochemical work of Jorpes and his colleagues 

 in Stockholm which appeared to show, beyond all reasonable doubt, that the 

 mast cell is the site of formation, or storage, of the anticoagulant, heparin. 

 Recalling my introduction to the mast cell, I obtained a sample of heparin 

 C Vitrum') from Stockholm in order to test its effect on mouse skin undergoing 

 carcinogenesis by 1, 2, 5, 6-dibenzanthracene. Heparin was repeatedly injected 

 under the precancerous skin in small doses in one group, and was painted on 

 excised wounds in the epilated areas of skin in a second group. However, 

 the results were disappointing. There was neither a definite promotion nor 

 a definite retardation of tumour formation in either group when comparison 

 was made with suitable controls. 



In 1944 Cramer and Simpson published their careful study of the mast-cell 

 reaction in precancerous mouse skin and reviewed the literature. These workers 

 brought forward one additional piece of evidence which at least seemed to show 

 that many of the mast cells in precancerous mouse skin do differ qualitatively 

 from normal mast cells. They noticed that the more superficial mast cells tend to 

 lose their metachromatism rather easily in a watery fixative and that many of 

 them, in frozen sections, exhibit a golden-brown fluorescence in ultra-violet light. 



During the present study I have returned repeatedly to this puzzling 

 phenomenon and have re-cut, stained and reviewed many of my old sections of 

 mouse skin in various stages of carcinogenesis and have examined the topical 

 effect of still other hydrocarbons dissolved in a non-irritant solvent, acetone. 

 The results are consistent. A polycyclic hydrocarbon capable of inducing 

 epilation, epithelial hyperplasia and the development of a mast-cell reaction in 

 the underlying dermis is carcinogenic. As Orr (1938) has pointed out, the 

 dermal changes spread gradually deeper and include the breaking up of the 

 refractile collagen bundles, changes in the elastica, fibroplasia and the accumula- 

 tion of tissue mast cells (Figs. 61-63). Orr, however, states that the mast-cell 

 reaction is not specific for carcinogenesis and in his later papers seldom 

 mentions it again. 



For a time I was content to believe that this local mastocytosis merely 

 reflects the increased and continuing fibroblastic activity in the dermis, as in 



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