[Experimental teratological studies on facial anomalies induced in mice by bis(dichloroacetyl)diamine. II. Pathogenesis of bis(dichloroacetyl)diamine-induced median cleft face syndrome in mice].

The present study was performed to clarify the pathogenesis of bis(dichloroacetyl)diamine (abbreviated as bisdiamine hereafter)-induced median cleft face syndrome in mice. Bisdiamine was administered by oral intubation to pregnant Jcl: ICR mice at a dosage of 3,200 mg/kg/day at days 7.5 and 8.5 of gestation (VP = day 0). Embryos were recovered at 4, 12, 24, 48, 72 and 96 hr after bisdiamine treatment at day 8.5 of gestation and morphological differences between the bisdiamine-treated and control embryos at the specific time intervals were quantitatively examined by the light and scanning electron microscopy. First, bisdiamine caused extensive death of cranial, mainly prosencephalic and mesencephalic, neural crest cells and neuroepithelial cells. Second, the former damage resulted in reduced numbers of mesenchymal cells in the frontonasal prominences and the latter resulted in dorsolateral deviation of the nasal placodes. Consequently, the medial nasal prominences were abnormally widely spaced and then, the median cleft face syndrome was induced. In addition, the findings suggesting that bisdiamine might cause aberrant movement of neural crest cells and/or mesenchymal cells were observed.