Detection of dominant lethal mutation in mice after repeated low-dose administration of 6-mercaptopurine.
Detection of dominant lethality after repeated low-dose administration was investigated, using the base analog 6-mercaptopurine (6-MP). The compound was administered to groups of 30 outbred CD-1 male mice by i.p. injection at dosage levels of 12.5, 25.0, or 50.0 mg/kg/day 5 days a week for 8 weeks. At the end of treatment, each male was cohoused for 1 week with two untreated females of different strains: one CD-1 and one (C3H x C57BL/10)F1. Negative (solvent) and positive (triethylenemelamine, TEM) control groups were included. Implant data were analyzed statistically. Exposure of male mice to 6-MP at 50 mg/kg/day resulted in 93% mortality and severe weight loss of the survivors. Body weights were also reduced in the group given 25 mg/kg/day. At the lowest dose level of 12.5 mg/kg/day, 6-MP had no noticeable toxic effect on the treated males. Dominant lethal analysis of the implant data showed that a statistically significant increase in dead implantations was induced in CD-1 but not in (C3H x C57BL/10)F1 females. The dominant lethal effect of TEM, the positive control, was detected in both strains of females tested.
D000818:Animals; D005799:Genes, Dominant / Q000187:drug effects; D005804:Genes, Lethal / Q000187:drug effects; D015122:Mercaptopurine / Q000633:toxicity*; D051379:Mice; D009153:Mutagens
D009153:Mutagens; D015122:Mercaptopurine