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 carcinoma may be limited by the fact it creates resistance cells. However, we have observed a remarkable decrease in certain types of drug resistance in patients treated with direct electric current. Experimental studies were therefore performed in animals to determine the differences in pharmacodynamics between chemotherapy with and that without electric treatment. Tumors were created in BALB/c mice by intradermal injection of 0.25 ml 4 x 10(6) Colon 26 cells/ml in the abdomen. Seven days later the mice were divided into two groups: controls and those that underwent electric treatment. Direct electric current (1,000 V, 0.2-0.8 microA) was passed between a platinum electrode inserted intradermally and the earth during and for 1 h after a single intravenous injection of 5-fluorouracil (5-FU; 12.5 mg ml(-1) kg(-1)). Peripheral blood samples were collected before and 5, 10, 20, 30, 45, and 60 min after the injection of 5-FU. Concentrations of 5-FU in the sera and tissues were measured by HPLC. The intratumoral concentrations of 5-FU in the electric treatment group were higher than those in the controls (P<0.05, two-factor analysis of variance), but the serum concentrations were not statistically different 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.
Ito
K
K
Department of Surgery, School of Medicine, Nagoya University, Japan. katsuki@tsuru.med.nagoya-u.ac.jp
Wong
L
L
Ando
H
H
Hibi
K
K
Hidemura
K
K
Kasai
Y
Y
Akiyama
S
S
Nakao
A
A
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D004599:Electric Stimulation Therapy; D005472:Fluorouracil / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil