Tofani S, Barone D, Berardelli M, Berno E, Cintorino M, Foglia L, Ossola P, Ronchetto F, Toso E, Eandi M
Department of Medical Physics, Ivrea Hospital, ASL 9, 10015 (TO), Ivrea, Italy.
Pharmacol Res. 2003 Jul;48(1):83-90.
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.
先前的研究表明，暴露于3 mT以上的静态和极低频（ELF）磁场（MF）会减缓免疫缺陷小鼠皮下移植的人类肿瘤的生长动力学，降低其转移能力并延长小鼠存活时间。在本文报道的实验中，将患有鼠Lewis肺癌（LLC）或B16黑色素瘤的免疫活性小鼠暴露于MF，并分别用两种常用抗癌药物进行治疗：顺二氨二氯铂（顺铂）和N，N-双（2-氯乙基）四氢-2H-1,3,2-恶唑磷-2-胺2-氧化物（环磷酰胺）。实验终点为存活时间。接受顺铂（3mg/kg腹腔注射）并暴露于MF的小鼠的存活时间明显（P<0.01）长于仅接受顺铂治疗或仅暴露于MF的小鼠，叠加了接受10mg/kg腹腔注射该药物的小鼠的存活时间，表明MF与药物治疗具有协同作用。相反，当用环磷酰胺（50mg/kg腹腔注射）治疗的小鼠暴露于MF时，未观察到协同作用，存活曲线与仅用该药物治疗的小鼠完全相同。与仅给予两种已知药物的小鼠相比，单独暴露于MF或与顺铂或环磷酰胺治疗一起暴露的任何小鼠均未出现临床症状或毒性。在用顺铂治疗的小鼠中发现MF协同作用的一个可能解释是，铂离子刺激自由基产生，而MF增强活性氧产生，导致肿瘤细胞膜通透性改变，对药物摄取产生积极影响。另外，或者除此之外，已经证明MF局部产生自由基会增加顺铂转化为能够与DNA结合的反应性物种的速率。
