Methotrexate resistance is due to: (A) Depletion of folate, (B) Overproduction of DHFRase, (C) Overproduction of thymidylate kinase, (D) Decreased DHFR ase
Answer is B. Mechanism for Methotrexate resistance Impaired transpo of Methotrexate into cells Production big altered forms of DHFR that have decreased affinity for the inhibitor Increased concentrations of intracellular DHFR through gene amplification Decreased ability to synthesize Methotrexate polyglutamtes Increased expression of a drug reflux transpoer, of MRP class Refer Goodman Gilman 11/e p1336