Pathogenesis of cyclophosphamide-induced fetal anomalies

Wendler, D

doi:10.1007/978-94-011-6654-6_6

Cited by 2 publications

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References 38 publications

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“…Also, since lysosomes do not appear in differentiating mesenchymal cells during normal development, their appearance following CP-treatment must be considered abnormal. A similar abnormal lysosomal response in the mesenchymal cells following CP treatment has been observed in the developing brain (Wendler, 1979;Mirkes et al, 1981;Greenaway et al, 1982), tooth (Orams, 19831, and limb buds (Schweichel and Merker, 1973;Manson et al, 1982), and in cleft palate induced by other chemicals (Ferguson, 1978;Shah et al, 1984;. In numerous other studies, a transient appearance of lysosomes in different embryonic tissues following administration of various teratogens has been noted (Jurand, 1966(Jurand, , 1968Schweichel and Merker, 1973;Morriss, 1973;Merker et al, 1975;Langman and Cardell, 1978;Ferguson, 1978;Merchant-Larios and Coello, 1978;Peters et al, 1979;Abramovici et al, 1980;DeSesso, 1981).…”

Section: Discussionsupporting

confidence: 73%

Differentiation of cyclophosphamide‐treated hamster secondary palate: Ultrastructural and biochemical observations

Shah

1990

Am. J. Anat.

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A study was undertaken to analyze the ultrastructural aspects and the enzyme acid phosphatase cytochemistry and biochemistry of the pathogenesis of cyclophosphamide (CP)-induced cleft palate in hamster fetuses. The initial CP-induced alterations were the appearance of lysosomes in the mesenchymal cells of the vertically developing palatal primordia within 8 hr of drug administration. The mesenchymal lysosomal activity, which increased during the next 16 hr, was abnormal and interpreted as a sub-lethal response to CP treatment. Subsequently, the lysosomal activity in the mesenchyme diminished gradually and, 48 hr after CP treatment, was absent. At this time, lysosomes were seen in the epithelial cells of the vertical palate. Fifty-six hours after CP treatment, unlike controls where palatal shelves were already fused, lysosomal activity subsided in the epithelial cells. Changes, however, continued to be seen at the epithelial-mesenchymal interface. These changes were characterized by discontinuity in the basal lamina, and by epithelial-mesenchymal contacts. They persisted for 8 hr but were absent thereafter. Sixty-four hours after CP administration, the vertical shelves became horizontal and remained so until term. Following analysis of data, both from the literature and from the present study, it was suggested that CP first affected mesenchymal cell proliferation, and then its cytodifferentiation, during the critical phase of early vertical development; consequently the reorientation of the shelves to a horizontal plane was delayed, inducing cleft palate.

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Section: Discussionsupporting

confidence: 73%

Differentiation of cyclophosphamide‐treated hamster secondary palate: Ultrastructural and biochemical observations

Shah

1990

Am. J. Anat.

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Cyclophosphamide effects on fetal mouse cephalic acetylcholinesterase

1988

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Pregnant C3H mice were exposed to a teratogenic dose of cyclophosphamide (CP, 20 mg/kg body weight) on the 10th day after copulation. Embryos or fetuses were examined 2-9 days later for gross abnormalities, weighed, and assayed for cephalic acetylcholinesterase (EC 3.1.1.7, AChE) activity, and haemoglobin content. In embryos examined 2 days after CP administration, fetal weight and brain weight were less than controls, but cephalic AChE was higher (p less than 0.001). The higher cephalic AChE was associated with a higher absorbance for haemoglobin, although at 14 days there was no apparent difference in the cephalic AChE and absorbance for haemoglobin, compared with controls. At 19 days, fetal weight, brain weight and brain AChE activity were less than controls (p less than 0.001 in each case). The raised cephalic AChE activity in 12-day embryos is explained by the presence of blood, which appears to have resorbed by day 14, whereas the reduced brain AChE activity in 19-day fetuses is accounted for by the growth inhibitory effects of the drug.

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Pathogenesis of cyclophosphamide-induced fetal anomalies

Cited by 2 publications

References 38 publications

Differentiation of cyclophosphamide‐treated hamster secondary palate: Ultrastructural and biochemical observations

Differentiation of cyclophosphamide‐treated hamster secondary palate: Ultrastructural and biochemical observations

Cyclophosphamide effects on fetal mouse cephalic acetylcholinesterase

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