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Effects on Mouse Blastocysts of in Vitro Exposure to Methylnitrosourea and 3-Methylcholanthrene¹

Department of Pathology and Northwestern University Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611

Mouse blastocysts were exposed in vitro to various concentrations of N-methyl-N-nitrosourea and 3-methylcholanthrene. The incorporation of [³H]thymidine, [³H]uridine, and [³H]leucine into the exposed blastocysts was determined either immediately following exposure or after 18 hr of culture. The concentrations of N-methyl-N-nitrosourea or 3-methylcholanthrene used had no effect on blastocyst viability in either situation. There was a concentration-dependent decrease in the incorporation of the precursors into blastocysts exposed to N-methyl-N-nitrosourea which appears to be more pronounced after 18 hr in culture. This effect was not demonstrated for 3-methylcholanthrene, which requires metabolic activation for reactivity. Blastocysts exposed to N-methyl-N-nitrosourea were injected into the uterine horns of surrogate mothers; a significant increase in the resorption rate of these blastocysts was seen when compared with controls. Similar experiments were performed to determine birth rate. A dose-dependent decrease in birth rate was observed which correlated well with the effects on incorporation of thymidine, uridine, and leucine but not with the effect on implantation rate.

¹ This investigation was supported by USPHS Grant 1R01Ca 29675-01 awarded by the National Cancer Institute, Department of Health and Human Services, and by Earl M. Bane Biomedical Research Fund.

² To whom requests for reprints should be addressed.

Received 10/20/81. Accepted 12/ 2/81.