Experiences with the dominant lethal test in female mice: effects of alkylating agents and artificial sweeteners on pre-ovulatory oocyte stages.
Pre-ovulatory oocytes are especially sensitive to mutagenic influences. Since post-dictyotene oocytes are not subject to selection and elimination before fertilization, they may reveal mutagenic effects directly and unrestrictedly. Presuming that a chemical is administered at pro-estrus to female mice one can conclude that the substance or its active metabolite has the chance to reach the gamete during the sensitive pre-fertilization stages. We proved the usefulness of the test system by investigating the effects of alkylating agents. A second step was to investigate other substances. The following treatments induced dominant lethal effects: methyl methanesulfonate 100 mg/kg i.m., cyclophosphamide 200 mg/kg per os, triaziquone 0.25 mg/kg i.p. In contrast, the following agents were ineffective and can be classified as not mutagenic in this method: sodium cyclamate 10 000 mg/kg per os, saccharine sodium, 10 000 mg/kg per os, cyclohexamine sulfate 150 mg/kg per os, ethanol 5 ml/kg per os.
D000818:Animals; D003338:Corpus Luteum; D003494:Cyclamates / Q000633:toxicity; D003520:Cyclophosphamide / Q000633:toxicity*; D010064:Embryo Implantation / Q000187:drug effects; D004971:Estrus; D005260:Female; D005313:Fetal Death; D005799:Genes, Dominant / Q000187:drug effects; D005804:Genes, Lethal / Q000187:drug effects; D051379:Mice; D009153:Mutagens; D009865:Oocytes / Q000187:drug effects*; D010063:Ovum / Q000187:drug effects*; D011247:Pregnancy; D011359:Proestrus; D012439:Saccharin / Q000633:toxicity; D014228:Triaziquone / Q000633:toxicity
D003494:Cyclamates; D009153:Mutagens; D003520:Cyclophosphamide; D014228:Triaziquone; D012439:Saccharin