Activity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts.

Background: RH1 and MeDZQ represent novel aziridinylbenzoquinones that can be activated by DT-diaphorase to form unique DNA lesions. RHI is due to enter a phase I clinical trial in the United Kingdom in the summer of 2003, where pharmacodynamic monitoring of DT-diaphorase will be performed. Materials and Methods: The antitumour efficacy of RH1 and MeDZQ has been studied in 4 human xenografts (3 non-small cell lung cancer and 1 colon cancer), and compared to the level of constitutive DT-Diaphorase activity measured by the DCPIP assay. Results: The 4 xenografts exhibited a wide range of DT-diaphorase activity (4.8 - 303 nmol/min/mg). Greater antitumour activity was recorded in the xenografts expressing high levels of DT-diaphorase (e.g. NX002, DT-diaphorase activity, 303 ± 52 nmol/min/mg, T/C to MeDZQ, 33.3% and to RH1, 43.4%). Conclusion: These data add in vivo support to a role for DT-Diaphorase in the antitumour activity of RH1.