Pg. Forkert et M. Moussa, TEMPORAL EFFECTS OF 1,1-DICHLOROETHYLENE ON NONPROTEIN SULFHYDRYL CONTENT IN MURINE LUNG AND LIVER, Drug metabolism and disposition, 21(5), 1993, pp. 770-776
Administration of 1,1-dichloroethylene (DCE) to mice evokes cytotoxici
ty involving Clara cells in lung, and at higher doses, centrilobular h
epatocytes in liver. Our objective is to investigate temporal alterati
ons in nonprotein sulfhydryl [glutathione (GSH)] content in lung and l
iver after administration of a dose of DCE (125 mg/kg). Contribution o
f GSH from whole blood comprised 54% and 14% of the amounts found in l
ung and liver, respectively, of DCE-treated mice, and were taken into
account to determine tissue content of GSH. In lung, a significant dec
rease in GSH (60% of control) was first detected at 6 hr, and levels r
emained low from 8 to 12 hr. In liver, a 50% decrease was initially de
tected at 1 hr after DCE treatment. Progressive increases were found t
hereafter, with a return to the control level at 24 hr. Histochemical
staining for GSH in liver revealed homogeneous labeling in hepatocytes
across the lobule; DCE treatment diminished staining uniformly in all
hepatocytes. In control lung, histochemical reactivity was exhibited
in bronchiolar epithelium and alveolar septa. Clara cells were stained
to the greatest extent and with considerable variability, whereas sta
ining was more uniform in alveolar septa. Staining was markedly dimini
shed by DCE treatment, and was initially abolished in the alveolar sep
ta, but retained to a limited extent within a small number of Clara ce
lls. These findings suggest that susceptibility of a subpopulation of
Clara cells to cytotoxicity may be associated, in part, with low expre
ssion of nonprotein sulfhydryl content at the time of DCE treatment.