Pharmacodynamics induced by direct electric current for the treatment of 5-fluorouracil resistant tumor: an animal experiment

The repeated use of chemotherapy to treat patients with colorectal carcinom a may be limited by the fact it creates resistance cells. However, we have observed a remarkable decrease in certain types of drug resistance in patie nts treated with direct electric current. Experimental studies were therefo re performed in animals to determine the differences in pharmacodynamics be tween chemotherapy with and that without electric treatment. Tumors were cr eated in BALB/c mice by intradermal injection of 0.25 ml 4x10(6) Colon 26 c ells/ml in the abdomen. Seven days later the mice were divided into two gro ups: controls and those that underwent electric treatment. Direct electric current (1000 V 0.2-0.8 muA) was passed between a platinum electrode insert ed intradermally and the earth during and for 1 h after a single intravenou s injection of 5-fluorouracil (5-FU; 12.5 mg ml(-1) kg(-1)). Peripheral blo od samples were collected before and 5, 10, 20, 30. 45, and 60 min after th e injection of 5-FU. Concentrations of 5-FU in the sera and tissues were me asured by HPLC. The intratumoral concentrations of 5-FU in the electric tre atment group were higher than those in the controls (P <0.05, two-factor an alysis of variance), but the serum concentrations were not statistically di fferent between the two groups. Pharmacodynamic changes were thus observed as a result of electrostatic treatment during chemotherapy. This elevated 5 -FU concentration in the tumor tissue is considered one of the reasons for the effective inhibition of 5-FU resistance in clinical cases.