Ostrovskaia L A, Bliukhterova N V, Fomina M M, Rykova V A, Korman D B, Burlakova E B
Emanuel Institute of Biochemical Physics, Russian Academy of Science, Moscow, 119991 Russia.
Radiats Biol Radioecol. 2003 May-Jun;43(3):273-81.
Biological effect of doxorubycin in standard (10(-3) mol/l) and ultra low doses (10(-5)-10(-20) mol/l) against some "signal" animal tumor systems--Lewis lung carcinoma, 755 adenocarcinoma, B-16 melanoma, Ehrlich carcinoma and L1210 leukemia was studied. The all models were very sensitive to the action of the drug in standard dose. Solid tumors' growth inhibition by 80-95% as well as increasing in life span of mice with L1210 leukemia by 86% in comparison with control and surviving of animals with Ehrlich carcinoma had been revealed. It had been shown that the drug in the area of ultra low doses occurred the following effects: inhibition of Lewis lung carcinoma growth by 80-95% compared to control after administration of the all tested ultra low doses; increasing of the life span of the animals with Ehrlich carcinoma and L1210 leukemia by 86-123% and 6-23%, correspondingly, upon the action of all tested ultra low doses; inhibition of B-16 melanoma growth by 50 and 70% after administration of the drug in doses 10(-20) mol/l and 10(-5) mol/l, correspondingly as well as deceleration of 755 carcinoma growth by 40% compared to control after action of the drug in the dose 10(-20) mol/l; stimulation of the B-16 melanoma growth by 20% relative to control after 10(-10) mol/l dose injection and enhancement of tumors sizes by 20-60% above control levels as a result of treatment of mice with 755 carcinoma by the drug in such ultra low doses as 10(-5) and 10(-15) mol/l. So, it was found that all tested tumor systems revealed certain sensitivity to the some ultra low doses of the drug. At the same time it was shown that doxorubycin in ultra low doses displayed alternative character of its biological effect, directivity of which varied according with the dose level and tumor strain.
研究了阿霉素在标准剂量(10⁻³mol/L)和超低剂量(10⁻⁵ - 10⁻²⁰mol/L)下对一些“信号”动物肿瘤系统——Lewis肺癌、755腺癌、B - 16黑色素瘤、艾氏癌和L1210白血病的生物学效应。所有模型对标准剂量药物的作用都非常敏感。已发现实体瘤生长抑制率达80 - 95%,与对照组相比,L1210白血病小鼠的寿命延长86%,艾氏癌动物存活。结果表明,在超低剂量范围内,该药物产生了以下效应:与对照组相比,在给予所有测试的超低剂量后,Lewis肺癌生长抑制率达80 - 95%;在所有测试的超低剂量作用下,艾氏癌和L1210白血病动物的寿命分别延长86 - 123%和6 - 23%;在分别给予10⁻²⁰mol/L和10⁻⁵mol/L剂量的药物后,B - 16黑色素瘤生长抑制率分别为50%和70%,与对照组相比,在给予10⁻²⁰mol/L剂量的药物作用后,755腺癌生长减缓40%;在注射10⁻¹⁰mol/L剂量后,相对于对照组,B - 16黑色素瘤生长刺激20%,在给予10⁻⁵和10⁻¹⁵mol/L等超低剂量的药物治疗小鼠后,755腺癌肿瘤大小比对照水平增大20 - 60%。因此,发现所有测试的肿瘤系统对该药物的某些超低剂量都表现出一定的敏感性。同时表明,超低剂量的阿霉素表现出其生物学效应的交替特性,其方向性随剂量水平和肿瘤菌株而变化。