mercaptopurine and Fetal-Resorption

A dominant-lethal test of 6-mercaptopurine (Spofa, CSSR) was carried out in male mice with four intraperitoneal, two oral, and one subcutaneous dosage levels. Furthermore, the drug was administered either in single doses or repeatedly for 7 and 14 consecutive days. With all of the dosage levels as well as administration durations and routes a genetic risk was proved at the periods of meiotic division and late premeiotic stages of spermatogenesis, manifested by increased percentages of fetal resorptions. In relationship to the total dose administered, irrespective of the route of administration, the most marked effect increasing the frequency of resorptions within the specified period of spermatogenesis was found in the groups that had received, by repeated administrations, more than 5.5 mg of 6-mercaptopurine per one male. Fertility reduction was apparent mainly after intraperitoneal injection; the differences were significant in weeks 3--5 of the test. The prenidation loss figures brought no univocal information about the interrelationship between the genetic effect and the stages of spermatogenesis.

Topics: Animals; Dose-Response Relationship, Drug; Female; Fertility; Fetal Resorption; Male; Mercaptopurine; Mice; Mice, Inbred Strains; Pregnancy; Time Factors

Dominant-lethal assays in male mice were made with the following cytostatics: Cyclophosphamide, TS-160, Edikron, Penberol, Cytembena, Mercaptopurine, Butocin, and Damvar. The cytostatics were administered mostly for 14-day periods, with the exception of Butocin (7 days) and high doses of Cyclophosphamide and TS-160 (single administrations). From the first day of administration on, the males were mated with intact females mostly at eight one-week intervals, and the quality of pregnancy was checked. Antifertility effects were found with TS 160, Penberol (at high dosage), and Mercaptopurine. Effects on permiogenesis with genetic risk were found with Cyclophosphamide, TS-160, Mercaptopurine, and less marked ones also with Cytembena. The effects were mostly manifested by increases in the numbers of early fetal resorptions, and less frequently by preimplantation loss of ova. No genetic risk was revealed by the assay in the cytostatics Edikron, Penberol, Butocin, and Damvar.

Topics: Acrylates; Alkylating Agents; Animals; Antimetabolites, Antineoplastic; Cyclophosphamide; Drug Evaluation, Preclinical; Female; Fetal Resorption; Infertility, Male; Male; Mercaptopurine; Mice; Mutagens; Nitrogen Mustard Compounds; Pregnancy; Spermatogenesis