Dominant-lethal test of 6-mercaptopurine: dependence on dosage, duration and route of administration

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.