mercaptopurine and Muscular-Atrophy

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.

Topics: Animals; Animals, Newborn; Behavior, Animal; Body Weight; Female; Male; Mercaptopurine; Muscular Atrophy; Rats; Rats, Inbred Strains; Species Specificity

In this study, male and female Sprague-Dawley rats were treated neonatally with 6-MP-treatment (2 mg/kg s/c, between 2 and 22 days after birth) and evaluated at six months of age. Compared to the normal controls, the 6-MP-treated male and female rats showed similar sciatic nerve conduction to the soleus. However, there was a significant muscle atrophy (57-60%, P less than 0.01) and a decrease in areas of the type I (42-54%, P less than 0.05) and type II (41-71%, P less than 0.01) muscle fibers. The number of type II fibers declined significantly (7.4-14.8%, P less than 0.05). It is proposed that the soleus muscle atrophy and histopathology in 6-MP-treated rats is unrelated to nerve conduction defects and may be related to growth inhibition caused by an interference of the drug during normal differentiation of muscle fibers.

Topics: Animals; Body Weight; Female; Male; Mercaptopurine; Muscle Contraction; Muscles; Muscular Atrophy; Neural Conduction; Organ Size; Rats; Rats, Inbred Strains

Topics: Animals; Animals, Newborn; Calcium; Electrolytes; Male; Mercaptopurine; Muscle Contraction; Muscles; Muscular Atrophy; Organ Size; Rats; Rats, Inbred Strains

This study was conducted to examine the histochemical changes occurring due to neonatal 6-mercaptopurine (6-MP) treatment (2 mg/kg, sc, between 2 and 22 days after birth) in the slow-twitch muscle (soleus) of adult male and female rats. At 6 months of age, the control and the 6-MP-treated rats were evaluated for the sciatic nerve conduction to the soleus and for the soleus atrophy and histopathology of the type I (slow-twitch) and type II (fast-twitch) muscle fibers. Compared to the normal controls, the 6-MP-treated male and female rats showed similar sciatic nerve conduction to the soleus. However, there was a significant muscle atrophy (57-60%, P less than 0.01) and a decrease in fiber areas of the type I (42-54%, P less than 0.05) and type II (41-71%, P less than 0.01) fibers. The number of type II fibers declined significantly (7.4-14.8%, P less than 0.05). It is proposed that the soleus muscle atrophy and histopathology in 6-MP-treated rats is unrelated to nerve conduction defects and may be related to growth inhibition caused by an interference of the drug during normal differentiation of muscle fibers.

Topics: Adenosine Triphosphatases; Animals; Female; Male; Mercaptopurine; Muscles; Muscular Atrophy; Neural Conduction; Rats; Sciatic Nerve

In previous studies, we found that Sprague-Dawley rats injected with 6-mercaptopurine monohydrate (6-MP) 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.

Topics: Animals; Animals, Newborn; Cricetinae; Female; Male; Mercaptopurine; Muscular Atrophy; Rats; Rats, Inbred Strains; Species Specificity

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.

Topics: Animals; Animals, Newborn; Body Weight; Female; Fertility; Hindlimb; Male; Mercaptopurine; Muscles; Muscular Atrophy; Paralysis; Rats; Rats, Inbred Strains