IT has long been recognised that tumours differ in their energy metabolism from normal tissues. Despite considerable investigation it is still not clear whether the altered energy metabolism is causally related to tumour development or merely secondary to the malignant state, although attempts to solve this problem have not been lacking (Weinhouse, 1955; Warburg, 1956;Weber, 1963). In this laboratory, we have been interested in three pyridine nucleotide-linked dehydrogenases, one from each of the principal pathways of glucose catabolism. The present status of each in relation to cancer biochemistry will be briefly reviewed.Lactate dehydrogenase (EC 1. 1.1. 27) LDH This enzyme catalyses the reversible reduction of pyruvate to lactate, the final step in anaerobic glycolysis. The product is known to accumulate in high concentration in many tumours (de Roetth, 1957; McBeth and Bekesi, 1962), and increased serum LDH activity is a feature of many tumour-bearing animals and human cancer patients (Wroblewski, 1958;1959 (Warburg, 1956), but this view has been strongly contested (Weinhouse, 1955). Activity of ICDH was increased in murine cervical cancers (Thiery and Willighagen, 1964) and in rat mammary cancers (Hilf, Michel,

Fr%:m the D c p r m e n t of I$iochcmistry, arid the L'ni-

No abstract

IN previous publications we have reported significant elevation of nucleases, adenosine deaminase and pyridine nucleotide-linked dehydrogenases in carcinoma of the human cervix uteri (Goldberg and Pitts, 1966; Ayre and Goldberg, 1966). These observations have been extended by study of another fibro-epithelial tissue with specialised function in the human female. Since the chosen tissue-the breast-is the site of pathological changes other than malignancy, the opportunity was taken to include these conditions within the scope of the investigation. MATERIALS AND METHODSFive samples of each of four histological types of human breast tissue were examined:Fibroadenomata.-These were removed as a solitary lesion from an otherwise healthy breast. The samples examined contained proliferating cells predominantly of mesenchymal origin, with moderate hyperplasia of acinar tissue. These changes were distributed throughout the lesion in a uniform manner. Three of the specimens were pericanalicular fibroadenomata and 2 were intracanalicular.Carcinomata.-One sample was a spheroidal cell carcinoma with pronounced malignant features. Another was an intra-duct carcinoma showing early invasion. The remaining 3 were scirrhous carcinomata displaying a moderate degree of mitotic aberration. The line of demarcation between normal and abnormal was imprecise, since none of the lesions was enc-apsulated. The sample cored out for examination was as free from fat and reactive fibrous tissue as was possible under the circumstances.NOTE. The following abbreviations will be used in the text and tables:RNA-ribonucleic acid DNA-deoxyribonucleic acid alk. and acid RNAase-alkaline and acid ribonuclease (EC 2.7.7.16) DNAase

PREVIOUS work in this Department has shown increased activities of certain dehydrogenases and nucleases in cancers of the human cervix uteri and breast (Goldberg and Pitts, 1966;Ayre and Goldberg, 1966;Goldberg, Pitts and Ayre, 1967). No differences were observed between simple breast tumours and normal tissue but many of the features found in the cancers were present in tissues showing diffuse epithelial hyperplasia. It seemed of considerable interest to determine whether these changes were generally characteristic of hyperplastic and neoplastic human epithelial tissues. The thyroid gland appeared a suitable organ in which to study the enzymological and cytochemical changes in which we were interested. Dow and Allen (1961), Schussler and Ingbar (1961), and Dumont and his associates (Dumont and Tondeur-Montenez, 1965; Dumont and Eloy, 1966; Dumont, 1966) have already presented evidence concerning the involvement of dehydrogenase enzymes and the energy pathways through which they operate in the metabolism of the thyroid gland in animals, although these studies have dealt mainly with the role of trophic hormones on various metabolic processes.The present communication is concerned with our observations on the activity and distribution of dehydrogenases in hyperplastic and neoplastic diseases of the human thyroid gland and on the effect of these diseases upon the distribution of protein in the cytoplasm. Data on the nucleases are presented in a second report (Goldberg and Goudie, 1968). MATERIALS AND METHODSThe thyroid tissues used for study of the distribution of enzymes and cytoplasmic protein were fresh surgical specimens obtained within 30 minutes of removal from 5 categories of subjects.Normal.-Eleven samples of histologically normal tissue were obtained from patients in whom the purpose of operation was removal of a thyroid adenoma or cancer.Thyrotoxic.-Twenty specimens were obtained from patients who pre-operatively had received antithyroid drugs and iodine. These glands showed epithelial hyperplasia and areas of focal thyroiditis. While these changes were fairly uniform within a single gland, considerable histological variation from one gland to another was encountered.