Enhanced X ray sensitivity of human colon tumor cells by combination of N-methylformamide with chemotherapeutic agents.
The responses of human colon tumor cells (clone A) to graded doses of x-irradiation were studied in combination with conventional chemotherapeutic drugs (bleomycin and 5-fluorouracil) after induction of commitment to differentiation by chronic exposure to N-methylformamide (NMF). NMF treated cells show increased radiation sensitivity, particularly in the low dose region of the survival curve. When doses of bleomycin (Bleo) and 5-fluorouracil (5-FU) were used that were subtoxic, both agents enhanced the cytotoxicity of x-irradiation by factors of about 1.25 and 1.10, respectively (at the 10% level of survival), and little sequence dependence was seen. However, in NMF treated cells, the combination of these drugs produced enhancement of X ray killing by factors of about 1.6 (x + bleo), 2.5 (bleo + x), 1.4 (x + 5-FU), and 1.6 (5-FU + x). Drug exposures were for 1 hr duration at 37 degrees C; 0.05 microgram/ml for Bleo, and 20 micrograms/ml for 5-FU. Since the X ray dose enhancement factor for NMF alone was about 1.3, the increased toxicity seen is probably additive in nature for the NMF + 5-FU + x experiments, but more than additive for the NMF + Bleo + x experiments. Also, complete removal of the shoulder was seen in the NMF + Bleo + X ray experiments. These data indicate that the use of differentiation-inducing agents in combination with other cytotoxic therapies might be important in yielding major decreases in the neoplastic cell burden, while avoiding the major morbidity seen in aggressive cancer therapy.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D005559:Formamides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques
D000970:Antineoplastic Agents; D005559:Formamides; D001761:Bleomycin; D005472:Fluorouracil; C002950:methylformamide