Static and ELF magnetic fields enhance the in vivo anti-tumor efficacy of cis-platin against lewis lung carcinoma, but not of cyclophosphamide against B16 melanotic melanoma.
Previous works showed that exposure to static and extremely low frequency (ELF) magnetic fields (MF) over 3 mT slows down the growth kinetics of human tumors engrafted s.c. in immunodeficient mice, reducing their metastatizing power and prolonging mouse survival. In the experiments reported here, immunocompetent mice bearing murine Lewis Lung carcinomas (LLCs) or B16 melanotic melanomas were exposed to MF and treated respectively with two commonly used anti-cancer drugs: cis-diamminedichloroplatinum (cis-platin) and N,N-bis (2-chloroethyl)tetra-hydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide (cyclophosphamide). The experiment endpoint was survival time. The survival time of mice treated with cis-platin (3mg/kg i.p.) and exposed to MF was significantly (P<0.01) longer than that of mice treated only with cis-platin or only exposed to MF, superimposing that of mice treated with 10mg/kg i.p. of the drug, showing that MF act synergically with the pharmacological treatment. On the contrary, when mice treated with cyclophosphamide (50mg/kg i.p.) were exposed to MF no synergic effects were observed, the survival curve being exactly the same as that of mice treated with the drug alone. No clinical signs or toxicity were seen in any of the mice exposed to MF alone or along with cis-platin or cyclophosphamide treatment, compared to mice given only the two known drugs.A possible explanation for the synergic effect of MF being found in mice treated with cis-platin could be that the platinum ion stimulates radical production and that MF enhance active oxygen production bringing about changes in tumor cell membrane permeability, influencing positively the drug uptake. Alternatively, or in addition to this, it has been demonstrated that the rate of conversion of cis-platin to reactive species able to bind to DNA, is increased by localized production of free radicals by MF.
Tofani
S
S
Department of Medical Physics, Ivrea Hospital, ASL 9, 10015 (TO), Ivrea, Italy.
Barone
D
D
Berardelli
M
M
Berno
E
E
Cintorino
M
M
Foglia
L
L
Ossola
P
P
Ronchetto
F
F
Toso
E
E
Eandi
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D002945:Cisplatin / Q000378:metabolism / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004574:Electromagnetic Fields; D005609:Free Radicals / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D055672:Static Electricity
D000970:Antineoplastic Agents; D005609:Free Radicals; D017382:Reactive Oxygen Species; D003520:Cyclophosphamide; D002945:Cisplatin