Handling of actinomycin D by preimplantation mouse embryos

• Published in: Experimental cell research Vol. 111; no. 1; pp. 117 - 126
• Main Authors: Epstein, C.J., Smith, S.A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 1978
• Subjects: Animals; Biological Transport; Blastocyst - drug effects; Blastocyst - metabolism; Dactinomycin - metabolism; Dactinomycin - pharmacology; Female; Kinetics; Mice; Ovum - metabolism; Temperature; Zona Pellucida - physiology
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/0014-4827(78)90242-2

Mouse embryos at the early blastocyst stage are much more sensitive to the lethal effects of actinomycin D at concentrations of ⩾0.1 μg/ml than are any of the other preimplantation stages. In the latter, concentrations of ⩾1 μg/ml prevent cleavage but do not cause cell death. This difference in sensitivity cannot be attributed to differences in the rate or extent of drug accumulation, since the less sensitive late blastocysts take up actinomycin D more rapidly and accumulate more than do the more sensitive early blastocysts. Earlier developmental stages accumulate actinomycin less rapidly and to a lesser total amount. The uptake process is not saturable under experimental conditions, with the rate of actinomycin D uptake being proportional to concentration up to 100 μg/ml. Following removal of embryos from the actinomycin, there is a gradual efflux of the drug, but significant amounts are still detectable within the embryos after 48 h. Although the zona pellucida does not affect actinomycin D uptake or efflux, temperature does have a marked effect. There is a 6- to 12-fold increase in rate of uptake between 24 and 37 °C, with a marked inflection or phase transition occurring at about 30 °C. This transition is much less prominent in unfertilized eggs, suggesting that a structural alteration in the membrane is produced by the fertilization process.