Histochemical changes in developing mouse liver after administration of phenobarbital Part of a dissertation submitted to the Horace H. Rackham School of Graduate Studies of the University of Michigan in partial fulfillment of the requirement for the degree of Doctor of Philosophy. Supported by N.I.H. grant GM 00312, Department of Anatomy, The University of Michigan, Ann Arbor, Michigan 48104.

Abstract

The effects of phenobarbital on development of some microsomal enzymes and neutral lipid were studied in mouse liver during a period of rapid cell differentiation. Specific alterations attributable to phenobarbital were identified in developing liver and used as markers for the onset of certain aspects of cell maturation. This investigation was designed to determine (1) the earliest developmental age at which fetal liver can react to phenobarbital and (2) the nature of the alterations in developing and adult liver. Intraperitoneal injections of phenobarbital were given for three days to 14, 17 and 19 day pregnant mice. Histochemical techniques were used to localize neutral lipid and the activities of NADPH diaphorase, glucose-6-phosphatase, and glucose-6-phosphate dehydrogenase. Total cell lipid was measured in livers from 17- and 19-day pregnant mice and livers from their fetuses. The density of reaction product for NADPH diaphorase and glucose-6-phosphate dehydrogenase increased while glucose-6-phosphatase decreased in adult liver. Similar changes were seen in livers from day-19 fetal animals but not in fetuses of younger ages. Neutral lipid droplets increased in size and number after phenobarbital in fetal mice of day 19 of gestation but not in mice of day 17 of gestation. It was concluded that liver from day-19 fetal mice had gained the competence, lacking in earlier ages, to respond to phenobarbital by increased production of some enzymes and neutral lipid.