Abstract
Acetazolamide sodium, a diuretic in man due to inhibition of carbonic anhydrase, produces postaxial forelimb deformities in mice when administered in utero on days 9 or 10 of gestation. The deformities are much more common on the right side. We have evaluated the pattern of mesenchyme cell aggregation and cartilage formation in day 11½ to 12½ forelimbs of C57BL/6J embryos, a strain known to be susceptible to this teratogen (Teratology 11:37, 1975). In d. 11½ forelimbs, in which aggregation of mesenchyme is normally not visible, there was no limb deformity and no necrosis of tissue. By d. 12 there is absence of the postaxial aggregates of either digits 4 and 5 or the ulna or both in the forelimbs, primarily the right. The remaining aggregates showed normal patterns of cell polarity, as determined by staining the Golgi apparatus with silver nitrate and determining the orientation of the stained mesenchyme cells toward the center of the aggregate. The mechanism of action of acetazolamide is not known. These studies suggest that it interferes with early mesenchyme cell aggregation in a restricted anatomic region presumably by interrupting the normal process of cell-to-cell adhesion.
Supported by N.I.H. Grants HD09689 and HL18714 and a grant from the C.H. Hood Foundation, Boston.
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Holmes, L., Trelstad, R. 915 ACETAZOLAMIDE- INDUCED FORELLMB MALFORHATION. Pediatr Res 12 (Suppl 4), 516 (1978). https://doi.org/10.1203/00006450-197804001-00920
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DOI: https://doi.org/10.1203/00006450-197804001-00920
