A dual effect of carcinogenic amines on protein metabolism in liver

Abstract

In short-term experiments the carcinogenic amines 2-aminofluorene, dimethylnitrosamine and p-dimethylaminophenylazoquinoline affect the protein metabolism of rat liver cells in two opposite directions: 1. 1. Within the first few hours a tendency towards a reduced activity of amino acid incorporation predominates. This effect is especially striking in experiments with liver slices incubated in vitro with the carcinogenic compounds. The inhibition is less marked in cell-free incorporation systems prepared from carcinogen-treated animals, and it is counteracted by a high dietary level of vitamin E. The effect is accompanied by a reduced proportion of ribosomal aggregates in the cytoplasm. Experiments with artificial messenger (polyuridylic acid) indicate that the inhibition is not only due to a loss of messenger RNA from the ribosomes but to a reduced functional ability of the particles. 2. 2. A few hours later the incorporation activity is stimulated, often far beyond the normal level. The stimulation is adrenal-dependent, and in starved animals it is accompanied by an increased glycogen deposition. The experiments suggest that under the influence of carcinogenic amines liver cells may become more sensitive to the systemic level of glucocorticoids. In short-term experiments in vivo the balance between the inhibitory and stimulatory phases varies with the nature of the carcinogen. The experiments suggest that both vitamin E deficiency and glucocorticoids may amplify the primary cytotoxic effect by rendering the coupling less tight between components of the detoxicating enzyme system in the endoplasmic membranes.