THE INTERACTION OF ETHANOL AND VITAMIN-A AS A POTENTIAL MECHANISM FORTHE PATHOGENESIS OF FETAL ALCOHOL SYNDROME

The mechanism of the fetal embryopathology resulting from ethanol inge stion during pregnancy is not established. This review summarizes rece nt research on the interaction of ethanol and vitamin A in models that explore if an interaction between these two compounds might potential ly be the mechanism for fetal alcohol syndrome. The rationale for this hypothesis includes the known facts that: (1) in adults, ethanol inge stion alters vitamin A metabolism and tissue distribution; (2) there a re many phenotypic similarities between fetal alcohol syndrome and mal formations of both vitamin A toxicity and deficiency; and (3) the vita min A metabolite, retinoic acid (RA), is a potent mediator in embryoge nesis and differentiation. One interaction that could possibly alter f etal development is that the synthesis of RR from retinol, catalyzed b y alcohol dehydrogenase, might be competitively inhibited by ethanol l eading to RA deficiency. Controversy over this hypothesis continues. A nother model demonstrates in vivo effects of pregnant rat mother's eth anol consumption on retinol, retinyl ester, RA content, RA receptor (R AR) binding, and the levels of RAR expression in developing fetal orga ns. The variable responses in this model still need clarification, and specific defects resulting from specific RAR changes have not yet bee n identified. In a quail embryo model, ethanol treatment mimics vitami n A deficiency, and RA appears to prevent the adverse effects of ethan ol. Finally, RA and ethanol reverse or block each other's effects in s tudies on isolated neuroblastoma cells. Taken together, these experime nts show definite interactions between ethanol and vitamin A. Further studies are needed to determine if any of these mechanisms significant ly contribute to prenatal ethanol consumption embryopathy; but, clearl y this hypothesis is gaining experimental support.