MGMT and neoplasm: Other factors might include: the rates of recovery of MGMT activity following depletion; tumor cell proliferation rates; the contribution of other protective mechanisms to cell survival; the relatively lower affinity of MGMT for free bases compared with O6-alkylguanines in duplex DNA [9,27]; poor water solubility; low bioavailability, instability and/or catabolic processes and rapid plasma clearance [28].