Henry T. Meriwether

Tissue distribution and storage forms of vitamin B12 injected and orally administered to the dog.

Summary 1. The distribution of oral and intravenous Vit. B12 was determined simultaneously in dogs using vitamin preparations labeled respectively with cobalt-57 and cobalt-60. 2. Thirty-one days after administration, the ratio of Co57/Co60 was constant in all tissues, indicating the existence of a common pool for cobalamin and related compounds regardless of mode of administration. 3. Conversion of administered labeled Vit. B12 to a noncyano form was demonstrated by reverse isotope dilution analysis of livers. This is true regardless of mode of administration. 4. It is suggested that chemical changes in the vitamin account in part for the complex excretion pattern of labeled Vit. B12.

Stability of Injected Vitamin B12-Co60 and Vitamin B12 Content of Dog Liver

Summary Vit. B12-Co60 injected intravenously into dogs is retained by dog livers as an intact cobalamin, probably as cyanocobalamin. This was demonstrated by the method of reverse isotope dilution. Direct isotope dilution indicates an average total cobalamin concentration of 0.36 μg/g of dog liver. The authenticity of retained Vit. B12-Co60, introduced by injection, as an isotope dilution tracer was demonstrated by simultaneous analysis with Vit. B12-CO57. Degradation of Vit. B12 to ionic, cobalt is negligible. The authors are greatly indebted to Mrs. Helen R Skeggs, Merck Sharp & Dohme Research Laboratories, for microbiolcgical assays. They wish to acknowledge the assistance of Mr. P. G. Gethard from these same laboratories for certain isolations and measurements contributing to Table II.

Experiences with tritiated compounds prepared by exposure to tritium gas.

The Random Tritiation of organic compounds by contact with curie quantities of tritium gas [1] has greatly simplified the labeling of many organic compounds. Despite the absence of an adequate theory for predicting the specific activity attainable with a particular substance, the method has proven successful in labeling a great variety of compounds, including biologically active materials such as ribonucleic acid, lysozyme [2], and insulin [3]. In the Merck Sharp & Dohme Research Laboratories, this technique has been employed for the tritium labeling of a steroid, many substituted aromatic compounds, a partly saturated polycyclic structure, a poly-basic amino acid, a porphyrin-like structure, a sugar phosphate, and, in confirmation of an earlier report, [1] sucrose. Conditions prevailing during the tritiation of these compounds, as well as specific activities attained, are listed in Table I.