Cellular responses to O,O,S-trimethyl phosphorothioate-induced pulmonary injury in rats.
O,O,S-Trimethyl phosphorothioate (OOS-TMP), an impurity of many organophosphorus insecticides, causes a delayed toxicity in rats and mice which is associated with morphological and biochemical changes in the lung. Oral administration of doses as low as 20 mg/kg alters bronchiolar epithelial morphology and causes an increase in bronchopulmonary lavage lactate dehydrogenase levels. In the present study, the effects of OOS-TMP on alveolar and bronchiolar cells were examined by determining the patterns of cellular regeneration in rats at periods of 12 hr, 24 hr, 3 days, and 7 days after treatment. Dividing cells were labeled with tritiated thymidine and studied with autoradiographic techniques. The results showed that OOS-TMP treatment initiated proliferation of alveolar type II cells within 24 hr. The proliferative response of type II cells continued to increase in 3-day and 7-day treatment groups. Labeled alveolar type I cells began to appear after 3 days, indicating that type II cells were dividing to replace damaged type I cells. Cells of the alveoli were thickened and showed vacuolization. In the bronchioles, labeled Clara cells were increased on Day 3 and Day 7 while the number of labeled ciliated cells remained near control levels throughout all time points, indicating that in bronchiolar epithelium, OOS-TMP stimulates the proliferation of Clara cells but does not damage ciliated cells. The binding of tritiated OOS-TMP to lung tissue was also examined by autoradiography. It was found that [3H]OOS-TMP binds to all regions of lung tissue.
D000818:Animals; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D063086:Organothiophosphates / Q000378:metabolism / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D014316:Tritium; C019123:O,O,S-trimethyl phosphorothioate