Butylated hydroxytoluene (BHT)-mediated increases in NAD(P)H-quinone oxidoreductase (QR) in mouse lung: Evidence for the alveolar type II cell as a site of QR activity

Abstract

Administration of butylated hydroxytoluene (BHT) to inbred A J mice increased lung cytosolic NAD(P)H-quinone oxidoreductase (QR) activity. Increased QR activity was observed using a dose of BHT of 100 mg/kg ip, although maximal increases in activity were observed following BHT 300 mg/kg ip. Increased lung QR activity could be observed as early as 24 hr post-BHT (300 mg/kg ip). Bronchiolar Clara cells and pulmonary macrophages isolated using an elastase digestion procedure from both control and BHT-treated mice exhibited minimal QR activity. The majority of basal and BHT-increased QR activity remained in the undigested lung. As isolation of many cell types to a high degree of purity from mouse lung is not yet feasible, QR activity was measured in established mouse lung cell lines and in cell isolates from rat lung. QR activity was low in a Clara tumor cell line, but higher activity was observed in three alveolar type II cell lines. Type II cell-enriched populations isolated from rat lung exhibited sixfold greater QR activity than the remaining undigested lung. Pulmonary QR activity was significantly greater in rat than in A J or C57 mice. Treatment of cultured Clara or type II cells with BHT in vitro did not increase QR activity.