Effect of zidovudine on human fetal lung development.

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Effect of zidovudine on human fetal lung development.

Pediatr AIDS HIV Infect. 1995 Apr;6(2):83-90. Unique Identifier : AIDSLINE AIDS/95368380
DiMaio MF; Ting A; Hsu MT; Gil J; Kattan M; Jack and Lucy Clark Department of Pediatrics, Mount Sinai School; of Medicine, New York, New York, USA.

Abstract: 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)

Keywords: Cell Differentiation/DRUG EFFECTS Epithelium/CYTOLOGY/DRUG EFFECTS/EMBRYOLOGY Fetus/*DRUG EFFECTS Human In Vitro Lung/CYTOLOGY/*DRUG EFFECTS/*EMBRYOLOGY Microscopy, Electron Organ Culture Photomicrography Pulmonary Alveoli/CYTOLOGY/DRUG EFFECTS/EMBRYOLOGY Support, U.S. Gov't, P.H.S. Zidovudine/*PHARMACOLOGY JOURNAL ARTICLE

951130
M95B0930

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