Studies on Isolated Tumour Mitochondria: Biochemical Properties of Mitochondria from Hepatomas with Special Reference to a Transplanted Rat Hepatoma of the Solid Type

Abstract

A BASIC policy in the study of neoplastic growth is to compare the metabolic characteristics of a tumour with those of the homologous normal tissue. In the long run this may lead to a better understanding of the neoplastic diseases and furnish some rational clue(s) for a chemotherapy of cancer.The rat liver is a suitable tissue for study because of its relatively uniform composition, the ease of obtaining a sufficient quantity of tissue and the possibility of inducing experimental hepatomas with chemical agents. In the experiments to be reported in the present paper, mitochondria were isolated from a transplanted rat hepatoma and studied in respect to a number of important enzymic reactions. The original tumour (case No. BY 252) arose several years ago in a rat of our inbred colony as a result of feeding DAB*. The following favourable circumstances allow that a strict comparison can be made between the enzymic activities of the hepatoma and normal liver mitochondria. The intraperitoneally transplanted BY 252 rat hepatoma is composed of a uniform population of undifferentiated liver tumour cells classified as a carcinoma solidum. Since fibrous elements are virtually absent, the tumour shows the same softness as normal rat liver and homogenization of the two types of tissue can thus be performed in exactly the same way.The levels of the free and DNP-activated ATPases, oxidative phosphorylation in the absence and presence of thyroxine and fatty acid oxidation of the hepatoma particles have been studied. The results of these experiments clearly showed that the hepatoma mitochondria were more labile in vitro than normal rat liver mitochondria.Another transplanted rat hepatoma which has become a favourite test object in recent years is the Novikoff hepatoma (Novikoff, 1957). The latter tumour and the BY 252 hepatoma show approximately the same rate of growth and a similar histological structure; both have been induced by DAB. According to the Greenstein concept, undifferentiated tumours, as a class, tend to resemble each other metabolically more than they do their tissue of origin (Greenstein, 1953(Greenstein, , 1956). The pertinent data on which this concept is based, apply not only to metabolic functions performed by organo-typical enzyme systems-such as those mediating the formation of urea in the liver-but also to enzymes which are * Abbreviations are used as follows: DAB =p-dimethylaminoazobenzene, AAT = o-aminoazotoluene, ATP -= adenosine triphosphate, DNP -= 2,4: dinitrophenol, DPN = diphosphopyridine nucleotide, NAA = nicotinamide, EDTA = ethylenediamine tetra-acetate, a-OC = a-oxycaproato.

Preparation and Properties of Mitochondria from Ehrlich Ascites Tumor Cells

“…Moreover, Emmelot et oi. (6) have also found a partly latent ATPase in the mitochondrial fraction of the Ehrlich ascites tumour. The anomalous results of the Hungarian workers are probably due to the omission of Mg 2+ from their reaction medium.…”

“…references I and 2), relatively few papers have appeared concerning the oxidative phosphorylation of the isolated mitoehondria of these cells (3)(4)(5)(6). The reason for this is probably largely a technical one: the ascites cell has a very tough cell membrane and the procedure generally used for homogenizing animal tissues--with a loosely fitting PotterElvehjem homogenizer in isotonic s u c r o s e -i s not sufficient to break the tumour cells.…”

Deficiency of Uncoupler-Stimulated Adenosine Triphosphatase Activity in Tightly Coupled Hepatoma Mitochondria

“…3). Similarly, intact mitochondria isolated from several rapidly growing hepatomas by Emmelot et al (21) and Devlin and Pruss (22) also fail to elicit a normal uncoupler-activated ATPase activity. The DNP-stimulated ATPase activity of mitochondria from these various hepatomas is compared in Fig.…”

Qualitative and Quantitative Ultrastructural Analysis of the Mitochondria from Adrenal Gland Cortex Under the Action of Viperidae family Snake Venoms

“…These details agree with the analysis presented here, since the number of mitochondrial cristae per mitochondrion and the numbers of mitochondria per unit area were apparently unrelated. The thesis that the amount of mitochondria is reduced in different pathologies was supported by biochemical studies, which observed this phenomenon in hepatocytes, due to low respiratory capacity (Emmelot et al, 1959). Such a metabolic restriction would not only imply a decrease in the secretion of cortisol, and other corticosteroids, but a decrease in the concentration of aldosterone.…”