Isolation and Rationale for the Formation of Isomeric Decarbamoylmitomycin C- N⁶-deoxyadenosine Adducts in DNA.

ABSTRACT: Mitomycin C (MC) is an anticancer agent that alkylates DNA to form monoadducts and interstrand cross-links. Decarbamoylmitomycin C (DMC) is an analogue of MC lacking the carbamate on C10. The major DNA adducts isolated from treatment of culture cells with MC and DMC are N²-deoxyguanosine (dG) adducts and adopt an opposite stereochemical configuration at the dG-mitosene bond. To elucidate the molecular mechanisms of DMC-DNA alkylation, we have reacted short oligonucleotides, calf thymus, and M. luteus DNA with DMC using biomimetic conditions. These experiments revealed that DMC is able to form two stereoisomeric deoxyadenosine (dA) adducts with DNA under bifuntional reduction conditions and at low temperature. The dA-DMC adducts formed were detected and quantified by HPLC analysi

SUBMITTER: Zacarias O 

PROVIDER: S-EPMC7061421 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature