The metabolism of isolated rat-liver nuclei.

The investigations described in this paper were undertaken as a preliminary to the study of the biochemical changes in the nucleus of the rat-liver cell during the induction of liver cancer. Allfrey (1954) and Stern & Mirsky (1953) described the isolation in aqueous media of nuclei from the thymus gland of the calf. Such preparations in vitro incorporated glycine and other amino acids into nuclear proteins (Allfrey, Mirsky & Osawa, 1955), and orotic acid and adenosine into the ribonucleic acid fraction of the nucleus (Allfrey & Mirsky, 1957). No comparable studies have been carried out on rat-liver nuclei. However, Logan, Ficq & Errera (1959), using radioautographic techniques, have shown that isolated rat-liver nuclei will take up phenylalanine and adenine in vitro. There is considerable doubtabout themechanisms whereby the nucleus obtains its energy supply. Evidence so far obtained points to some form of oxidative phosphorylation (Allfrey & Mirsky, 1957), but the nature of the oxidative pathway involved is still unknown. In this paper the chemical composition of isolated rat-liver nuclei has been determined, and protein and nucleic acid syntheses have been investigated. The effects of anoxia, 2:4-dinitrophenol, chlorpromazine and azide on these reactions have been studied. Investigations of the adenosinetriphosphatase activities of the preparations coupled with the results of the synthetic experiments have thrown further light on the underlying energy mechanisms of the nucleus.