LC-MS/MS coupled with stable isotope dilution method for the quantification of 6-thioguanine and S(6)-methylthioguanine in genomic DNA of human cancer cells treated with 6-thioguanine.

ABSTRACT: Thiopurines, including mercaptopurine (MP), 6-thioguanine ((S)G) and azathioprine, are widely used for the treatment of many human diseases including acute lymphoblastic leukemia (ALL). To exert their cytotoxic effect, these prodrugs need to be metabolically activated to (S)G nucleotides and incorporated into nucleic acids. (S)G in DNA can be methylated spontaneously to S(6)-methylthioguanine (S(6)mG) in the presence of S-adenosyl-l-methionine. It was proposed that S(6)mG, owing to its high miscoding potential (pairing preferentially with thymine), may induce cell death by triggering the postreplicative mismatch repair pathway. Understanding the implications of this pathway in the cytotoxic effect of thiopurine drugs necessitates an accurate measurement of the level of S(6)-methylthio-2'-d

SUBMITTER: Wang H 

PROVIDER: S-EPMC2922690 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature