Alcohol dehydrogenase and ethanol tolerance at the cellular level in Drosophila melanogaster.

Exposure of early third instar larvae of Drosophila melanogaster to a nonlethal dose of ethanol was detrimental to larvae lacking alcohol dehydrogenase (ADH) but beneficial to wild-type larvae in terms of surviving a later ethanol tolerance test, indicating that one of the important functions of the ADH system is to supply derivatives of ethanol to larvae that in turn promote ethanol tolerance. High intracellular concentrations of ethanol in ADH-deficient (Adhn2) larvae fed ethanol were accompanied by a decrease in the cell membrane infoldings of fat body cells, suggesting that the capacities to absorb and release molecules were reduced. Marked effects of ethanol on the endoplasmic reticulum and mitochondria of ADH-deficient larvae were also evident. The absence of similar changes in wild-type larvae that were fed moderate levels of ethanol showed that the ADH system kept the intracellular level of ethanol at a concentration low enough to avoid cell damage. A cytometric analysis of electron micrographs showed that there were ethanol-induced reductions in glycogen, lipid, and protein stores in the fat body cells of ADH-deficient larvae fed 1.25% ethanol (v/v) compared with null larvae fed an ethanol-free diet. This finding implied that the capacities to synthesize or store these compounds may be limited by high intracellular concentrations of ethanol. The cytometric analysis also revealed that the consumption of diets containing 2.5% and 4.5% ethanol by Canton-S wild-type larvae for 3 days after 4 days of feeding on an ethanol-free diet resulted in decreases in glycogen and protein deposits in fat body cells, but increased the amount of lipid deposits compared to larvae fed an ethanol-free diet. This observation, coupled with the greater weight of wild-type adults that were fed a growth-limiting concentration of ethanol compared with control adults, suggested that a metabolic defense mechanism in larvae is to convert toxic ethanol to nontoxic storage products. Dietary ethanol alone and in combination with isopropanol stimulated an increase in the size of the NAD-pool in larvae, a condition that may favor the activity of ADH. A low dietary level of isopropanol (1%) completely blocked glycogen deposition in wild-type larvae, whereas ethanol did not. Thus ethanol and isopropanol exert some different toxic effects on larval fat bodies.