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In these proceedings there has been a great deal about the effects of alcohol on biogenic amine metabolism and the possible role of biogenic amine condensation products in alcoholism. There has been little mention of how alcohol affects macromolecules, and indeed the literature is scanty in this problem area. The present report will deal with alterations in brain protein and nucleic acid metabolism as a function of chronic alcohol ingestion in the C57BL/6J mouse. Much of what will be discussed has appeared in press or soon will be.'-4 C57BL/6J male mice, a strain that prefers alcohol over water, were used in all these studies. The experimental animals received 10% (v/v) ethanol in water as their only drinking fluid, and their age-matched controls received only water. Unless otherwise indicated, l a t e r was substituted for the alcohol solution 24 hours before the mice were sacrificed. All animals were provided with laboratory chow, and under these conditions no infections, debility, or mortality were observed in either group even for periods extending to nine months. The alcoholdrinking animals were slightly heavier and had larger livers than the controls, but no differences in brain weights were observed between the two groups. When alcohol was removed, no signs of withdrawal reaction were noted. Subcellular fractionation and other biochemical procedures are given el~ewherel-~ and will not be repeated here.In FIGURE 1, the pH 5 enzyme content of brain is presented as a function of duration of alcohol consumption. This fraction is obtained from the cell sap and includes among other ingredients the initial components of the protein-synthesizing system, namely aminoacyl tRNA synthetases, tRNAs, and the transferases. The results show no differences between the fractions obtained after one or three days of alcohol consumption and fractions from controls. However, alcoholimbibing mice showed a slight decrease of the pH 5 enzyme content at 10 days; this decrease continued with duration of alcohol consumption, so that animals that had consumed alcohol for 46 days had about half as much pH 5 enzyme as controls.Brain ribosomes isolated from animals that had imbibed alcohol for 10 days were incubated in the presence of UJ4C leucine, pH 5 enzyme fraction, and various cofactors and ions. Comparisons were made at various time points with the same fractions obtained from control mice. The data in FIGURE 2 show a significant decrease in incorporation of UJ4C leucine in ribosomal protein of the fractions obtained from brains of alcohol-treated animals. A similar inhibition was noted when fractions were obtained from mice that had imbibed alcohol for 46 days.To determine whether inhibition in protein synthesis involves the pH 5 enzyme fraction, the ribosomes, or both, crossover experiments were performed. The results indicate no marked increase in leucine incorporation when ribosomes from control animals were substituted for ribosomes of ethanol-treated mice (FIGURE 3 ) . A substantial enhancement of incorporation occurred when ...

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The pharmacokinetic and pharmacodynamic effect of injecting into lipohypertrophic tissue is small in comparison to the usual clinical variation observed with insulin injections.