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- W2014488085 abstract "Cyclophosphamide adversely affects both prenatal and postnatal development of mice. Metabolites of this drug are alkylating agents. An in vitro system was developed and optimized with regards to pH, G6P, and NADP for the activation of cyclophosphamide by the 9000 g supernatant of livers from mature virgin female mice. The kinetics of cyclophosphamide activation were determined to assure zero-order kinetics. The same conditions were used to determine the ability of various perinatal tissues to metabolize cyclophosphamide. Neither the fetus nor the placenta was a major site for the generation of alkylating metabolites. A comparison of the activity in livers from late pregnant, nursing, male, and female mice indicated that the nursing mothers at 3, 7, 14, and 21 days after giving birth had greater ability to activate cyclophosphamide than mature virgin females. There were no significant differences between the remaining groups and female controls. Cyclophosphamide activation by neonatal livers at 1, 3, 5, 7, and 14 days after birth ranged between 10 and 30% of the activity found in female controls. There were no significant differences in activity between livers of 21-day-old neonates and mature females. Neonatal cyclophosphamide toxicity was demonstrated by following lethality and the growth of litters that received either the drug or vehicle at 24–48 hr after birth. The average body weights of treated litters were significantly less than controls from 5 days of age until the experiment was terminated 6–7 wk after treatment; 22 ± 17% of the cyclophosphamide-treated neonates succumbed compared to no deaths in controls. It was concluded that perinatal cyclophosphamide toxicity occurs at a time when the affected organism has not developed its ability to form alkylating metabolites." @default.
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- W2014488085 date "1971-05-01" @default.
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- W2014488085 title "Development of cyclophosphamide activation and its implications in perinatal toxicity to mice" @default.
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- W2014488085 doi "https://doi.org/10.1016/0041-008x(71)90194-3" @default.
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