title: Neonatal Clara cell toxicity by 4-ipomeanol alters bronchiolar organization in adult rabbits.
abstract: Nonciliated bronchiolar (Clara) cells metabolize environmental toxicants, are progenitor cells during development, and differentiate postnatally. Because differentiating Clara cells of neonatal rabbits are injured at lower doses by the cytochrome P-450-activated cytotoxicant 4-ipomeanol than are those of adults, the impact of early injury on the bronchiolar epithelial organization of adults was defined by treating neonates (3-21 days) and examining them at 4-6 wk. Bronchiolar epithelium of 6-wk-old animals treated on day 7 was most altered from that of control animals. Almost 100% of the bronchioles were lined by zones of squamous epithelial cells. Compared with control animals, the distal bronchiolar epithelium of 4-ipomeanol-treated animals had more squamous cells (70-90 vs. 0%) with a reduced overall epithelial thickness (25% of control value), fewer ciliated cells (0 vs. 10-20%), a reduced expression of Clara cell markers of differentiation (cytochrome P-4502B, NADPH reductase, and 10-kDa protein), and undifferentiated nonciliated cuboidal cell ultrastructure. We conclude that early injury to differentiating rabbit Clara cells by a cytochrome P-450-mediated toxicant inhibits bronchiolar epithelial differentiation and greatly affects repair.
authors.affiliation: Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis 95616-8732, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Smiley-Jewell
authors.forename: S J
authors.initials: SJ
authors.lastname: Nishio
authors.forename: A J
authors.initials: AJ
authors.lastname: Weir
authors.forename: C G
authors.initials: CG
authors.lastname: Plopper
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015415:Biomarkers; D001980:Bronchi / Q000187:drug effects* / Q000254:growth & development* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D004848:Epithelium / Q000648:ultrastructure; D005260:Female; D008168:Lung / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D011817:Rabbits; D013729:Terpenes / Q000506:poisoning*
chemical_list: D015415:Biomarkers; D013729:Terpenes; C001470:4-ipomeanol