X ray responses of a human colon tumor cell line after exposure to the differentiation-inducing agent N-methylformamide: Concentration dependence and reversibility characteristics

Abstract

The combination of differentiation-inducing agents with conventional cytotoxic agents has been suggested as a potential cancer therapeutic strategy. In this regard, we have chronically exposed (3 passages) a human colon tumor line (clone A) to varying concentrations (0–170 mM) of N-methylformamide and examined the change in sensitivity to ionizing radiation in vitro. The linear-quadratic formalism of survival was used to characterize the single graded dose survival curves. This equation yields two constants (α and β) relating to cellular inactivation produced by either single events (α) or by the combination of two events (β). As the N-methylformamide concentration increased, the a parameter increased while the β parameter concomitantly decreased, yielding a concentration dependent radiosensitization which was most marked in the low dose region of the survival curve. Upon removal of NMF, the original radiation resistance was regained within 2–3 cell culture doubling times.