Intraperitoneally injected ^<115m>lCd (4.4mg/kg of body weight as ^<115m>CdCl_2) was first transported into blood and almost simultaneously from blood to various tissues. The ^<115m>Cd concentration-time curves fitted a double two-compartment model which included two velocities for cadmium transfer. A general equation derived from this model was Y = A (e^<-k3t> - e^<-k1t>) + B (e^<-k4t> - e^<-k2t>), where Y is the amount of cadmium in μg/g of wet weight tissue, k_1 and k_2 are rate constants for in-flow to the tissue, k_3 and k_4 are rate constants for out-flow from the tissue, A and B are coefficients and t is time in min. During the first 30 min ^<115m>Cd concentration in blood of pregnant mice was almost the same as and there-after lower than that of non-pregnant mice. Equations for the blood cadmium concentration-time curves showed that the content of the compartment with slow cadmium turnover (S-compartment) in pregnant mice decreased to about a half of that in non-pregnant mice. Simultaneous injection of 7-day-pregnant mice with zinc (3.3 mg/kg of body weight as ZnCl_2) and ^<115m>Cd decreased the content of the compartment with fast cadmium turnover (F-compartment) and increased the content of the S-compartment in blood. However, the content of the S-compartment in the liver and kidneys was reduced by zinc administration as much as by 50 - 70% of that of the control mice (^<115m>Cd alone), while the content of the F-compartment was not significantly altered. It is suggested that cadmium transfer from blood to tissue through the S-compartment is suppressed by zinc. The ^<115m>Cd content of embryos from 12-day-pregnant mice was not predicted by the double two-compartment model. Little ^<115m>Cd was detected in embryos until 60 min after administration. After 120 min a moderate concentration of ^<115m>Cd was found in the embryos with placentas in which the metal heavily accumulated. No correlation was observed between fetal intrauterine position and the ^<115m>Cd content of the embryo or placenta with fetal membranes.

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Many problems as to the morphogenesis of cardiovascular malformations remain unsolved. The morphogenesis of a series of conotruncal anomalies presents particularly difficult problems. The authors administered bisdiamine to rats for the purpose of clarifying the morphogenesis of conotruncal anomalies, establishing their critical periods, and extrapolating these findings to the morphogenesis of cardiac malformations in man. We were able to induce numerous experimental cardiac malformations by singly administrating 200mg bisdiamine orally to rats on the 9th, 9.5th, 10th, and 11th day after conception. Among these cardiac malformations, 82.6% proved to be persistent truncus arteriosus and cardiac anomalies corresponding to tetralogy of Fallot in man, followed by 15.2% of aortic arch anomalies including vascular ring, right aortic arch, and aberrant subclavian artery. Extracardiac malformations observed included corneal extrusion, diaphragmatic hernia, cleft lip, and abnormal lobulation of the right lung. Thymus weight was significantly less than that of the control (P<0.001), with the gland showing in-sufficient lobulation and descent. Histologically, depletion of lymphocytes in the thymic cortex and loss of cortico-medullary demarcation was detected, being diagnosed as hypoplasia. The authors conclude from these findings that the malformation complex caused by administration of bisdiamine might be used as an experimental model of the DiGeorge syndrome. It is presumed that its critical period would correspond to the third to fourth week of gestation in man.

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Hydroxyurea (HU) was intraperitoneally administered to pregnant Wistar rats at a dose of 25, 50, 100 or 200 mg/kg/day during the organogenetic period (days 9 to 12 of gestation). utters from these dams were observed for their morphological and behavioral development. Eye abnormalities and dilated ventricles were found in the offspring of the 25-200 mg/kg/day groups. The development of the female righting reflex at 2 days of age in the 25 mg/kg/day group and the male free fall reflex in the 100 and 200 mg/kg/day groups was delayed. The number of rearing observed in the open field test was increased in the female group treated with 100 mg/kg/day of HU. No inhibition of rotorod performance was observed in all treated groups. The acquisition rate of conditioned avoidance response was not influenced by HU treatment. These findings suggested that under the present experimental conditions, HU induced both morphological abnormalities and behavioral disturbances in a wide dose range and that there was little difference between doses producing behavioral disturbances and morphological anomalies.

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