Muscular degeneration in rats after postnatal treatment with 6-mercaptopurine.

Abstract

6-Mercaptopurine monohydrate was injected sc at 2 mg base/kg/day from 2 to 22 days of age to four litters of rat pups (four females, four males per litter). Control neonates were injected sc with basic saline (pH 8). Daily observations for signs of toxicity were made during the treatment period and once weekly thereafter until the rats were 6 months of age. The pups were weighed at 2, 12, 23, 34, 100, and 480 days of age. Fertility was tested at 3 to 6 months of age. From 6 months of age on, the rats were examined for tumors at 3-month intervals until the experiment was terminated at 16 months of age. A reduction in body weight of treated rats began between 34 and 100 days of age and became more pronounced by 16 months of age. Fertility was similar in treated and control groups and there were no detectable tumors in either group. The major finding in treated rats was a delayed onset of hind leg paresis that was first detected at 12 months of age. Light microscopic examination of tissues taken from the hind quarters of these rats at 16 months of age revealed a severe atrophic degeneration with fatty infiltration of sublumbar and thigh muscles.