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The Use of Uterine Vascular Clamping in the Pregnant Rat to Modify the Embryotoxic Effects of Anticancer Drugs¹

Departments of Pediatrics, Radiology, and Medicine, The Stein Research Center, and Eleanor Roosevelt Research Laboratories of the Jefferson Medical College, Philadelphia, Pennsylvania 19107

The technic of isolating one horn of the pregnant rat uterus from the maternal circulation has been utilized to study the rapidity of action of cancer chemotherapeutic agents upon the developing embryo.

The eight- and nine-day-old rat embryo was the most suitable stage of gestation for studying the combination of uterine vascular clamping and the administration of anticancer drugs.

The four parameters that were utilized to evaluate the protective effect of uterine vascular clamping were the embryonic resorption rate, fetal growth retardation, incidence of congenital malformations, and fetal hematologic effects. The resorption rate was the most reliable parameter for measuring the protective effect of uterine vascular clamping. Although embryonic growth retardation was also a reliable parameter, the number of surviving embryos frequently was so small in one particular group that the weight data could not be utilized. Obtaining the incidence of malformations and the fetal blood counts was time consuming and yielded nondiscriminating results.

The combination of uterine vascular clamping plus the administration of nitrogen mustard, aminopterin, 5-fluorouracil, and 5-fluorodeoxyuridine demonstrated that the embryonic effect of the latter three drugs was ameliorated by isolating the pregnant uterus from the maternal circulation for 15 or 30 minutes. Surprisingly, the clamping technics did not protect against the lethal effects of nitrogen mustard. This was believed to be due to the persistence of clinical toxicity of this drug in the maternal rat.

The advantages and disadvantages of this technic are compared to other bioassay procedures. Since the interpretation of this bioassay procedure includes complex interrelationships between mother and embryo and many aspects of placental transfer, the practical usefulness of this bioassay procedure is limited to the determination of the biologic life span of cancer chemotherapeutic agents as they pertain to the embryo.

¹ Supported by NIH Research Grants HD-630 and CY-5287.

Received 9/ 7/67. Accepted 5/ 1/68.