Haswell-Elkins M R, Satarug S, Tsuda M, Mairiang E, Esumi H, Sithithaworn P, Mairiang P, Saitoh M, Yongvanit P, Elkins D B
Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
Mutat Res. 1994 Mar 1;305(2):241-52. doi: 10.1016/0027-5107(94)90244-5.
Cancers arising during bacterial, viral and parasitic infection provide useful models to investigate the link between inflammation and carcinogenesis. Because the inflammatory agent is known, relationships between immune responses, the production of DNA-damaging agents, such as nitric oxide, oxygen radicles and N-nitroso compounds, and cancer risk can be explored. This paper first describes the close relationship between infection with the liver fluke, Opisthorchis viverrini, and cholangiocarcinoma in humans. Data are then presented which demonstrate an elevation in levels of salivary nitrite and urinary and plasma nitrate among men with moderate and heavy liver fluke infections compared to uninfected controls which was absent 4 months after the parasites were cleared with praziquantel. Because of the strict control over subject selection and dietary intake plus the absence of the increase following treatment, we conclude that the higher levels of nitrate and nitrite reflect endogenous generation of nitric oxide resulting from liver fluke infection. Excess nitric oxide generation in the inflamed tissue is likely to lead directly to the formation of N-nitroso compounds mediated by activated macrophages. Further work will attempt to demonstrate a link between this increase and both parasite-specific immune responses and the risk of cancer.
在细菌、病毒和寄生虫感染过程中发生的癌症为研究炎症与致癌作用之间的联系提供了有用的模型。由于炎症因子是已知的，因此可以探索免疫反应、DNA损伤剂（如一氧化氮、氧自由基和N-亚硝基化合物）的产生与癌症风险之间的关系。本文首先描述了人类感染肝吸虫（华支睾吸虫）与胆管癌之间的密切关系。然后给出的数据表明，与未感染的对照组相比，中度和重度肝吸虫感染男性的唾液亚硝酸盐水平以及尿液和血浆硝酸盐水平有所升高，在用吡喹酮清除寄生虫4个月后这种升高消失。由于对受试者选择和饮食摄入进行了严格控制，加上治疗后没有出现升高，我们得出结论，较高水平的硝酸盐和亚硝酸盐反映了肝吸虫感染导致的内源性一氧化氮生成。炎症组织中过量的一氧化氮生成可能直接导致由活化巨噬细胞介导的N-亚硝基化合物的形成。进一步的研究将试图证明这种升高与寄生虫特异性免疫反应和癌症风险之间的联系。
