Johnke R M, Abernathy R S, Kovacs C J, Evans M J, Biggs L E, Daly B M, Loven D P
Department of Radiation Oncology, East Carolina University School of Medicine, Greenville, North Garolina 27858, USA.
Anticancer Res. 1997 May-Jun;17(3C):2169-74.
To determine whether non-hematologic tumors influence the bone marrow's antioxidant enzyme response to the radioprotective cytokine interleukin 1 alpha (IL-1), studies were undertaken using BDF1 and Balb/c mice bearing small, medium or large Lewis lung carcinoma (LLCa) or EMT6 mammary carcinoma tumors, respectively. Results demonstrated that, similar to nontumor-bearing mice, treatment of tumor-bearing animals with IL-1 was associated with a significant increase in marrow MnSOD activity. However, the duration of this elevated activity was reduced as tumor burden increased, and this reduction may have an impact on IL-1's ability to radioprotect tumor bearing animals, especially when tumor burden is large. In addition to cytokine-mediated responses, significant tumor-related influences on the marrow's antioxidant enzyme status were seen. Notably, it was observed that the presence of tumor was correlated with a marked suppression of antioxidant enzyme activity. Surprisingly, however, the pattern of enzyme suppression was found to differ between the two tumor models studied both in temporal onset and in the number of enzymes involved. In conclusion, the data obtained from these studies on tumor-bearing animals demonstrate that there are both cytokine-related and tumor-related influences which can effect the antioxidant enzyme status of the hematopoietic marrow-influences which may have the potential to alter the marrow's ability to tolerate free radical-generating events, both endogenous (i.e inflammation, infection) and exogenous (i.e. radiation, certain chemotherapeutic drugs) in origin.
为了确定非血液学肿瘤是否会影响骨髓对抗辐射细胞因子白细胞介素1α(IL-1)的抗氧化酶反应,研究人员分别使用携带小、中或大Lewis肺癌(LLCa)或EMT6乳腺癌肿瘤的BDF1和Balb/c小鼠进行了实验。结果表明,与未患肿瘤的小鼠相似,用IL-1治疗患肿瘤动物会使骨髓锰超氧化物歧化酶(MnSOD)活性显著增加。然而,随着肿瘤负荷增加,这种活性升高的持续时间缩短,而这种缩短可能会影响IL-1对患肿瘤动物的辐射防护能力,尤其是当肿瘤负荷较大时。除了细胞因子介导的反应外,还观察到肿瘤对骨髓抗氧化酶状态有显著影响。值得注意的是,发现肿瘤的存在与抗氧化酶活性的显著抑制相关。然而,令人惊讶的是,在所研究的两种肿瘤模型中,酶抑制模式在时间 onset 和涉及的酶数量方面均有所不同。总之,从这些对患肿瘤动物的研究中获得的数据表明,存在细胞因子相关和肿瘤相关的影响,它们可以影响造血骨髓的抗氧化酶状态——这些影响可能有潜力改变骨髓耐受内源性(即炎症、感染)和外源性(即辐射、某些化疗药物)产生自由基事件的能力。