[The influence of the N-mustard derivative "cytostasan" on pregnancy and fetal development in the rat].
This presentation describes the action of Cytostasan, a nitrogen mustard compound of benzimidazole, on reproduction and embryonic development of Wistar rats. Single doses from 20 through 100 mg/kg body weight were given intraperitoneally on the 4th, 7th, 9th, 11th or 13th day post coitum. All test animals were sacrificed on the 20th day of pregnancy. The following parameters served as a base for evaluation: the means of implantation rates, resorption rates, fetal body weights and the number of dead and living fetuses. Malformations were detected by outer inspection for gross anomalies, by means of the razor blade technique for malformations of organs and by alizarin preparations for detecting anomalies of the osseuos skeleton. All results were compared with those of an untreated control group and evaluated by statistical means. Cytostasan exerts embryotoxic and teratogenic effects in appropriate dosage. Notwithstanding the fact of giving high doses (1/2 LD 50) there is no loss of blastocysts before implantation: the number of implantation sites equals that of the control group. The resorption rate increases at all examined days of development after application of 40 mg/kg, but 20 mg/kg exert effects only on days 4, 7, and 11 p. c. There is no action on the number of living fetuses after injection of 20 mg Cytostasan/kg body weight. After application of 40 mg/kg the number of living fetuses decreases especially on the 7th, 9th, and 13th day p. c. There is a dose-dependent stunting: the fetal body weight is not reduced after a dosage of 20 mg/kg, but 40 mg/kg cause a considerable loss of weight during embryogenesis (days 9, 11, 13). It is impossible to induce stunting during blastogenesis (days 4 and 7). The observed patterns of malformation are relatively uniform: kinked tails, omphaloceles, hydronephroses, hydrocephali. Skeletal defects are absent. The results received are compared with other findings on aklylating antitumour drugs.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001562:Benzimidazoles / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D005333:Fetus / Q000187:drug effects*; D005865:Gestational Age; D009588:Nitrogen Mustard Compounds / Q000009:adverse effects*; D011247:Pregnancy; D051381:Rats; D013723:Teratogens
D001562:Benzimidazoles; D009588:Nitrogen Mustard Compounds; D013723:Teratogens
Uber die Beeinflussung von Schwangerschaft und Keimlings-entwicklung der Ratte durch das N-Lost-Derivat "Cytostasan"