Cytogenetic studies on preimplantation mouse embryos exposed to methylnitrosourea in vivo.
Since exposure of mice to methylnitrosourea (MNU) during the preimplantation period can induce malformations and an increased postnatal death rate, direct embryotoxic effects were studied in preimplantation embryos shortly after treatment of pregnant mice on days 2 and 3 of gestation with single i.p. injections of 2.5, 5.0, and 10.0 mg/kg MNU. Embryos exposed to MNU for 24 h after treatment on day 2 showed a significant reduction of cell number and induction of sister chromatid exchange (SCE) frequency, but no structural chromosomal aberrations or inhibition of development during culture. Embryos exposed to MNU in vivo for 3 h on day 3 showed significantly reduced cell numbers, a significant inhibition of development in culture, and an increase in structural chromosome aberrations. Due to the high cytotoxicity of MNU, determination of SCE was not possible. The results indicate that MNU reaches preimplantation mouse embryos shortly after maternal treatment and that malformations seen at term and postnatal effects are probably induced by the direct action of MNU on early embryos. Furthermore, the importance of the time interval chosen for evaluation of toxicologic endpoints in preimplantation embryos is demonstrated.
Vogel
R
R
Max von Pettenkofer Institut, Federal Health Office (BGA), Berlin, West Germany.
Granata
I
I
Spielmann
H
H
D000818:Animals; D001755:Blastocyst / Q000187:drug effects*; D002869:Chromosome Aberrations / Q000139:chemically induced* / Q000502:physiology; D025063:Chromosome Disorders; D005260:Female; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D009028:Morula / Q000187:drug effects; D011247:Pregnancy; D012854:Sister Chromatid Exchange / Q000187:drug effects
D008770:Methylnitrosourea