516 THE TOCOPHEROLS 



that the duration and degree of depletion necessary to bring about other 

 tissue dysfunctions have not been attained (as in the rabbit and in cattle), 

 or that only a deficiency state during early life of the species has been 

 studied (as in the mink, sheep, pig, horse, duck, turkey) and that little or 

 nothing is known of the effects of prolonged, chronic deficiency during adult 

 phases of life. 



c. Pigment 



Since frequent reference will be made to an acid-fast pigment often as- 

 sociated with lesions of vitamin E deficiency, it seems appropriate at this 

 point to discuss briefly its nature and possible origin. Martin and Moore^ 

 first called attention to the occurrence of this pigment in uterine smooth 

 muscle, skeletal muscle, sex glands, and other organs and tissues of rats 

 maintained for prolonged periods on low E diets, and commented on its 

 insolubility, inert and iron-free nature, and the brownish discoloration of 

 the affected tissues. Its brownish-yellow fluorescence was also recognized.^ 

 Although its major site of formation appears to be in the musculature, it 

 eventually comes to be acquired by macrophages of the adjacent connective 

 tissues and distributed rather widely throughout the reticulo-endothelial 

 system.*' ^ Chemical analysis of the pigment in rat uteri suggests the pres- 

 ence of oxidation products of protein. ^ Histochemical studies^ suggest a 

 lipofuchsin type of pigment derived through peroxidation and polymeriza- 

 tion of unsaturated fats; except for certain differences in its oxidation po- 

 tential, it is undistinguishable from a yellowish-brown, waxy pigment com- 

 monly observed in association with nutritional cirrhosis of rats on low 

 protein diets and first characterized by Lillie et al.,^ who proposed the term 

 "ceroid" for it. In paraffin sections of tissues exposed to various fixatives 

 and fat solvents, both pigments have similar acid-fast, sudanophilic and 

 other staining reactions. Recent histochemical studies^- ^ further support 

 the theory that ceroid arises through the autoxidation of unsaturated lipids 

 pathologically accumulated in cells having an insufficiency of biological 

 antioxidants. Victor and Pappenheimer^ have pointed out that failure to 



1 A. J. P. Martin and T. Moore, J. Hyg. 39, 643 (1939). 



2 T. Moore and Y. L. Wang, Biochem. J. 37 Proc. i (1943); Brit. J. Nutrition 1, 53 

 (1947). 



3K. E. Mason and A. F. Emmel, Yale J. Biol. Med. 17, 189 (1944). 



«K. E. Mason and A. F. Emmel, Anat. Record 92, 33 (1945). 



6 H. Elftman, H. Kaunitz, and C. A. Slanetz, Ann. N. Y. Acad. Sci. 52, 72 (1949). 



6 R. D. Lillie, L. L. Ashburn, W. H. Sebrell, F. S. Daft, and J. V. Lowry, Public 

 Health Repis (U.S.) 57, 502 (1942). 



7 W. G. B. Casselman, J. Exptl. Med. 94, 549 (1951). 



8 R. D. Lillie, Stain Technol. 27, 37 (1952). 



9 J. Victor and A. M. Pappenheimer, /. Exptl. Med. 82, 375 (1945). 



I 



