The energy relations of mitotic activity in adult mouse epidermis

Abstract

The theory that epidermal mitotic activity in the mouse involves significant quantities of energy has been examined in the relatively simple conditions of a saline tissue-culture medium. It is shown that an adequate oxygen supply is of the highest importance, both oxygen intake and mitotic activity varying directly with oxygen tension. In anaerobic conditions cell division ceases. Sufficient quantities of glucose must also be available in the medium, though pyruvate or lactate may be substituted. In the absence of such substrates respiration con­tinues actively, but mitosis is severely depressed. Such substances as glutamate, fumarate and citrate, when added in catalytic amounts, are capable of increasing both the rate of oxygen uptake and the rate of epidermal mitosis. It appears, therefore, that the substrates are oxidized by way of the tricarboxylic acid cycle, and that the energy so produced is needed to support mitosis. Substances such as cyanide, azide and malonate, which interfere with aerobic respiration, as well as iodoacetate and fluoride, which interfere with glycolysis, are powerful inhibitors of epidermal mitosis. Dinitrophenol, which interferes with aerobic phosphorylation, has a similar effect. The point of inhibition of all these substances, like that of oxygen lack, is in the antephase, which is just before the visible prophase. They are all without effect on any mitosis already in progress.