Supraadditive formation of micronuclei in preimplantation mouse embryos in vitro after combined treatment with X-rays and caffeine.

The influence of caffeine (0.1 or 2 mM), X-rays (0.24 Gy [= 25 R] or 0.94 Gy [= 100 R]), or of a combination of both on the formation of micronuclei in early stages of preimplantation mouse embryos in vitro was studied. X-rays as well as caffeine induced micronuclei. The dose-effect curve after irradiation was linear for the dose range measured (0-3.76 Gy; = 0-400 R). Caffeine did not induce micronuclei if the concentration was 1 mM or less; between 1 mM and 7 mM, however, there was a linear increase in the number of micronuclei. A considerable enhancement of the number of radiation-induced micronuclei was observed when irradiation of the embryos was followed by a treatment with caffeine. Not only was the sum of the single effects exceeded by the combination effects, but the combination results even lay in the range of supraadditivity of the envelope of additivity.