Pierson H F
Cancer Lett. 1985 Mar;26(2):221-33. doi: 10.1016/0304-3835(85)90030-8.
Groups of BDF1 and DBA mice were treated with either the cupric chelate of nitrilotriacetic acid (NTA-Cu+2) or the cuprous chelate of neocuproine (NC-Cu+1) every other day for 7 days prior to either i.p. or s.c. inoculation with 10(6) viable B16 melanoma cells, and then every other day for 15 days post-tumor inoculation. This treatment schedule was non-toxic to host mice. NC-Cu+1 acted as a tumor growth promoting factor in mice by enhancing tumorigenicity, stimulating body weight gain, inhibiting encapsulation of i.p. tumors that permitted growth as unrestrained ascites, and increasing final tumor weight over a shortened host survival period regardless of the site of tumor inoculation. Treatment with NTA-Cu+2 inhibited pigmentation in DBA mice bearing s.c. tumors, while treatment with NC-Cu+1 enhanced tumor pigmentation regardless of the site of tumor inoculation and murine strain. These results suggest that exogenous copper in the form of chelates alters the growth characteristics of a copper-requiring tumor system in both a copper-chelate- and murine-specific manner, and further suggests that the growth promoting activity of exogenous copper in the B16 melanoma system involves both enhanced copper nutrition and concomitant alteration of host reactions to tumors.
在经腹腔或皮下接种10⁶个活的B16黑色素瘤细胞之前7天，每隔一天用次氮基三乙酸铜螯合物（NTA-Cu²⁺）或新亚铜灵亚铜螯合物（NC-Cu⁺¹）处理BDF1和DBA小鼠组，共7天，然后在肿瘤接种后每隔一天处理15天。该治疗方案对宿主小鼠无毒。NC-Cu⁺¹通过增强致瘤性、刺激体重增加、抑制腹腔肿瘤的包囊形成（从而使肿瘤能以不受限制的腹水形式生长）以及在缩短宿主存活期的情况下增加最终肿瘤重量，而不论肿瘤接种部位如何，在小鼠中起到肿瘤生长促进因子的作用。用NTA-Cu²⁺处理可抑制皮下接种肿瘤的DBA小鼠的色素沉着，而用NC-Cu⁺¹处理则可增强肿瘤色素沉着，而不论肿瘤接种部位和小鼠品系如何。这些结果表明，螯合形式的外源性铜以铜螯合物和小鼠特异性的方式改变了需要铜的肿瘤系统的生长特性，并且进一步表明外源性铜在B16黑色素瘤系统中的生长促进活性涉及增强的铜营养以及宿主对肿瘤反应的伴随改变。
