Claussen U, Hettwer H, Voelcker G, Krengel H G, Servos G
Teratog Carcinog Mutagen. 1985;5(2):89-100. doi: 10.1002/tcm.1770050203.
After iv injection of cyclophosphamide (CP; 80 mg/kg) and dechlor-CP (60 mg/kg) on the 9th day of gestation (histiotrophic phase of nutrition) in rabbits, the concentrations of activated CP and activated dechlor-CP were determined fluorometrically in the maternal blood and in the yolk sac fluid. Activated CP and dechlor-CP could be measured in the maternal blood but not in the yolk sac fluid. This holds true for both the free as well as the protein bound form. During the histiotrophic phase of nutrition on the 9th day of gestation, the yolk sac wall seems to be a barrier for activated CP and dechlor-CP. This phenomenon has to be traced back on the oxazaphosphorinring activated in position C4 and not on the alkylating activity. Therefore, a direct effect of activated CP can be excluded as the main reason for the embryotoxicity of CP. Consequently, the effects of iv-injected CP on the entoderm of the visceral layer of the yolk sac placenta were investigated. Three, 6, 12, and 24 hours after CP injection, the maternal animals were laparotomized and the entoderm of the visceral layer of the yolk sac placenta in the mesometral parts of the blastoderms were prepared for electron microscopy. Like in the control group, 3 hours after CP injection no differences are found. Six hours after CP injection, a relatively flat cell-type can be observed, which is probably based on the reduced absorptive capability of the entoderm. Twelve hours after CP injection the entoderm cells are nearly uniformly of the columnar type; this is interpreted as a restored absorptive activity. Twenty-four hours after CP injection the columnar form of the entoderm cells and the reduced pinocytotic activity are interpreted as a state of secretion. During the histiotrophic phase of nutrition (9th day of gestation in rabbits), CP-induced inhibition of the absorptive activity of the entoderm cells might lead to a quantitatively and/or qualitatively changed nutrition of the developing embryo. This changed nutrition may be the source of the embryotoxic effects of CP.
在妊娠第9天（组织营养期）给家兔静脉注射环磷酰胺（CP；80mg/kg）和脱氯环磷酰胺（60mg/kg）后，采用荧光法测定母血和卵黄囊液中活化CP和活化脱氯环磷酰胺的浓度。在母血中可检测到活化CP和脱氯环磷酰胺，但在卵黄囊液中未检测到。游离形式和蛋白结合形式均如此。在妊娠第9天的组织营养期，卵黄囊壁似乎是活化CP和脱氯环磷酰胺的屏障。这种现象必须归因于在C4位活化的氧氮磷杂环，而非烷基化活性。因此，可排除活化CP的直接作用是CP胚胎毒性的主要原因。因此，研究了静脉注射CP对卵黄囊胎盘脏层内胚层的影响。CP注射后3、6、12和24小时，对母兔进行剖腹手术，制备胚盘系膜部卵黄囊胎盘脏层内胚层用于电子显微镜检查。与对照组一样，CP注射后3小时未发现差异。CP注射后6小时，可观察到一种相对扁平的细胞类型，这可能是由于内胚层吸收能力降低所致。CP注射后12小时，内胚层细胞几乎均为柱状类型；这被解释为吸收活性恢复。CP注射后24小时，内胚层细胞的柱状形态和胞饮活性降低被解释为分泌状态。在组织营养期（家兔妊娠第9天），CP诱导的内胚层细胞吸收活性抑制可能导致发育中胚胎的营养在数量和/或质量上发生变化。这种变化的营养可能是CP胚胎毒性作用的来源。
