<P> Accidental injection of vinca alkaloids into the spinal canal (intrathecal administration) is highly dangerous, with a mortality rate approaching 100 percent . The medical literature documents cases of ascending paralysis due to massive encephalopathy and spinal nerve demyelination, accompanied by intractable pain, almost uniformly leading to death . Several patients have survived after aggressive and immediate intervention . Rescue treatments consist of washout of the cerebrospinal fluid and administration of protective medications . Children may do better following this injury . One child, who was aggressively treated at the time of the injection, recovered almost completely with only mild neurological deficits . A significant series of inadvertent intrathecal vincristine administration occurred in China in 2007 when batches of cytarabine and methotrexate (both often used intrathecally) manufactured by the company Shanghai Hualian were found to be contaminated with vincristine . </P> <P> The overuse of vincristine may also lead to drug resistance by overexpression of the p - glycoprotein pump (Pgp). There is an attempt to overcome resistance by the addition of derivatives and substituents to the vincristine molecule . </P> <P> Vincristine works partly by binding to the tubulin protein, stopping the cell from separating its chromosomes during the metaphase; the cell then undergoes apoptosis . The vincristine molecule inhibits leukocyte production and maturation . </P> <P> Vincristine is created through the semi-synthesis coupling of indole alkaloids vindoline and catharanthine in the vinca plant . It can also now be synthesized through a stereocontrolled total synthesis technique which retains the correct stereochemistry at C18' and C2' . The absolute stereochemistry at these carbons is responsible for vincristine's anticancer activity . </P>

Vincristine acts on which phase of cell cycle