In vitro germ cell models for the detection of fertility impairment.
Pluripotent embryonic carcinoma cells and pluripotent embryonic stem cells established from undifferentiated cells of an early mouse embryo were investigated for induction of proliferation inhibition, sister chromatid exchanges (SCE) and single-strand breaks by treatment with various germ cell mutagens. The comparison of malignant cells with nonmalignant cells showed an increased sensitivity of nonmalignant cells independent of their state of differentiation. Mitomycin C (MMC) inhibited the proliferation of nonmalignant cells at a concentration of 10(-6) M but did not affect growth of the teratocarcinoma cell line P19. There were no differences between the investigated cell lines at a lower MMC concentration. At the concentration of 10(-6) M MMC the sister chromatid exchanges of P19 were enhanced up to 41 SCE per metaphase. Testing of another germ cell mutagen, ethylnitrosourea (ENU), gave similar results: a decreasing generation time of nonmalignant cell lines after treatment with 1 mM ENU and no effect on the teratocarcinoma cells. This concentration also induced a high number of SCE. Single-strand breaks could be produced by exposure to methanmethylsulphonate (MMS). 56.3% of embryonic stem cell DNA was passing through the filter after MMS treatment. In contrast to the embryonic stem cells, only 35.6% of teratocarcinoma DNA was affected.
Vogel
R
R
BgVV, Berlin, Germany. r.vogel@bgvv.de
Domke
A
A
Tenschert
B
B
Bremer
S
S
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005038:Ethylnitrosourea / Q000633:toxicity; D005298:Fertility / Q000187:drug effects*; D005854:Germ Cells / Q000187:drug effects*; D008741:Methyl Methanesulfonate / Q000633:toxicity; D051379:Mice; D016685:Mitomycin / Q000633:toxicity; D008954:Models, Biological; D009153:Mutagens / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D018243:Teratocarcinoma / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
D009153:Mutagens; D016685:Mitomycin; D008741:Methyl Methanesulfonate; D005038:Ethylnitrosourea