Development of phase II xenobiotic metabolizing enzymes in differentiatingmurine Clara cells

Glutathione S-transferases (GSTs) and epoxide hydrolases (EHs) protect cell s from exogenous insult by detoxifying electrophilic compounds. Little is k nown about these enzyme systems during postnatal lung development. This stu dy was designed to help establish whether the heightened neonatal susceptib ility of the lung to bioactivated cytotoxicants is the result of inadequate ability to detoxify reactive intermediates. We compared the distribution o f immunoreactive protein and enzymatic activity of GSTs and EHs in isolated distal airways during pre- and postnatal development in lungs of mice from 16 days gestation to 9 weeks postnatal age (adult). GST alpha, mu, and pi class protein expression in fetal and postnatal lung varied by isozyme and age. Isozymes alpha and mu are expressed at low levels before birth, high l evels on postnatal day 7, low levels between postnatal days 14 and 21, high levels at postnatal day 28, and slightly lower levels in adults. immunorea ctive protein of isozyme pi has a peak expression on gestational day 18 and again on postnatal day 4, is undetectable at postnatal day 21, and is at p eak levels in the adult mouse lung. CST activity in distal airways increase d with age. Microsomal EH protein expression increased in intensity with ag e, while activity was similar in airways from all ages. We conclude that in the mouse lung (1) cellular expression of glutathione S-transferase varies by age and isozyme and does not increase with increasing age, (2) airway g lutathione S-transferase activity increases with increasing age and does no t correlate with immunoreactive protein expression, and (3) airway microsom al epoxide hydrolase activity does not increase, even though immunoreactive protein expression does increase with age, (C) 2000 Academic Press.