Cellular responses to O,O,S-trimethyl phosphorothioate-induced pulmonary injury in rats

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Abstract

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.

References (26)

  • I.Y.R. Adamson et al.

    The pathogenesis of bleomycin-induced pulmonary fibrosis in mice

    Amer. J. Pathol.

    (1974)
  • I.Y.R. Adamson et al.

    Lung injury induced by butylated hydroxytoleune: Cytodynamic and biochemical studies in mice

    Lab. Invest.

    (1977)
  • W.N. Aldridge et al.

    The toxicological properties of impurities of malathion

    Arch. Toxicol.

    (1979)
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