X ray responses of a human colon tumor cell line after exposure to the differentiation-inducing agent N-methylformamide: concentration dependence and reversibility characteristics.
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 (alpha and beta) relating to cellular inactivation produced by either single events (alpha) or by the combination of two events (beta). As the N-methylformamide concentration increased, the alpha parameter increased while the beta 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.
Leith
J T
JT
Radiation Biology Laboratories, Brown University, Providence, RI.
Bliven
S F
SF
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004353:Drug Evaluation, Preclinical; D005559:Formamides / Q000627:therapeutic use*; D006801:Humans; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005559:Formamides; D011838:Radiation-Sensitizing Agents; C002950:methylformamide