Effect of zidovudine on human fetal lung development.
Zidovudine (AZT) is currently used to treat human immunodeficiency virus (HIV)-positive women during pregnancy to prevent the prenatal transmission of HIV type 1 (HIV-1). However, AZT not only inhibits HIV replication but also affects the DNA polymerases of human cells; hence AZT is not recommended during the first trimester of pregnancy. The lung is a unique organ because it continues to grow and develop throughout fetal life. Using a human fetal lung organ culture system, we sought to determine the effect of AZT on morphogenesis and epithelial cytodifferentiation of developing alveoli. Lung tissues from three fetuses, 14-15 weeks gestational age, were grown in culture for 24 hours (day 0). AZT at a concentration of either 0.4, 4.0, 8.0, or 40.0 mumol/L was added on days 1, 5, and 10 of growth. The cultures were interrupted on days 6 and 15 and examined by light and electron microscopy for alveolar saccular development, interstitial thinning, and epithelial cell differentiation. On day 6 of growth the treated cultures demonstrated fewer alveolar saccules and a thicker, more cellular interstitium compared to the controls. After 15 days of growth the cultures treated with 0.4 mumol/L of AZT appeared structurally similar to the controls. The cultures treated with AZT concentrations of 4.0 to 40.0 mumol/L appeared unchanged from day 6, implying arrested maturation of the culture. However, epithelial cell differentiation was unaffected. We conclude that AZT at concentrations of 4.0 mumol/L and greater affects the structural development of the human fetal lung in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
DiMaio
M F
MF
Jack and Lucy Clark Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA.
Ting
A
A
Hsu
M T
MT
Gil
J
J
Kattan
M
M
D002454:Cell Differentiation / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000196:embryology; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000196:embryology*; D008854:Microscopy, Electron; D009924:Organ Culture Techniques; D010784:Photomicrography; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D015215:Zidovudine / Q000494:pharmacology*
D015215:Zidovudine