Toxicological studies with 6-mercaptopurine in neonates

In previous studies, we found that Sprague-Dawley rats injected with 6-MP monohydrate at 2 mg base/kg sc daily from 2 to 22 days of age had atrophy of thigh and sublumbar muscles when killed at 16 months of age. The first sign of this muscle atrophy was detected grossly (flattened croup with or without paresis) at 12 months of age. In one experiment of the present work, using the same treatment in rats as above, we found that the earliest onset of muscle atrophy observed by light microscopy occurred at 2 months of age. By 4 months the atrophy could be detected grossly. The atrophy did not uniformly involve all muscles of the hindquarters; the thigh (especially the semitendinosus), leg (soleus but not the extensor carpi group), and lumbar vertebral (including the psoas) muscles were involved. Foreleg (biceps), intercostal, and tongue muscles as well as the sciatic nerve and internal organs appeared unaffected. In another experiment, weanling Sprague-Dawley rats given large daily doses of 6-MP from 25 to 45 days of age had normal muscles when killed at 8 months. In a third experiment, Wistar rats injected with 6-MP (2 mg base/kg sc) daily from 2 to 22 days of age and killed at 6 months had muscle atrophy similar to that seen in Sprague-Dawley rats. In the last experiment, mice and hamsters given large daily doses of 6-MP from 2 to 22 days of age had normal muscles when killed at 10 months. It appears from these results that the 6-MP-induced muscle atrophy occurs only after treatment during the neonatal period and that the atrophy may be species-specific.