Cancer initiation by fumonisin B1 in rat liver -: role of cell proliferation
Cancer initiation by fumonisin B1 in rat liver -: role of cell proliferation
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DOI：
10.1016/s0304-3835(01)00542-0
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发表时间：
2001-08-28
期刊：
影响因子：
9.7
通讯作者：
Wild, CP
中科院分区：
文献类型：
--
作者：
Gelderblom, WCA;Galendo, D;Wild, CP
伏马菌素B-1(Fumonisin B-1，FB1)是玉米枯萎病菌产生的一种致癌真菌毒素，其致癌机制与遗传毒性致癌物质相似，但动力学明显不同。本实验旨在评价肝部分切除(PH)和四氯化碳(CCl4)诱导的再生细胞增殖以及由硝酸铅(PbNO3)诱导的直接有丝分裂原诱导的增殖在FB1诱导的肿瘤发生中的作用。在14天内，FB1以不同剂量(0.14~3.5mgFB1/100g体重)灌胃给药，同时在FB1治疗开始后7天引入细胞增殖刺激，根据所使用的增殖刺激，在启动治疗结束3周后，通过2-乙酰氨基荧烯(2-AAF)治疗，然后在第4天给予PH或四氯化碳CCl4进行促癌作用。与PH和CCl4诱导的代偿性肝细胞增殖不同，FB1的致癌作用与肝脏毒性作用和脂质过氧化反应增加有关。有丝分裂原诱导的增殖(PbNO3)不能增强FB1的致癌潜能，这表明非遗传毒性致癌物的致癌作用是由再生细胞增殖支持的。在评估这种真菌毒素对人类构成的风险时，需要认识到FB1在启动癌症过程中促进细胞增殖的作用。(C)2001爱思唯尔爱尔兰科学有限公司。保留所有权利。
Fumonisin B-1 (FB1), a carcinogenic mycotoxin produced by the fungus Fusarium verticillioides in corn, causes cancer initiation in rat liver in a similar manner to genotoxic carcinogens although apparently with different kinetics. The present experiment was designed to evaluate the role of regenerative cell proliferation, effected by partial hepatectomy (PH) and carbontetrachloride (CCl4) and direct mitogen-induced hyperplasia, induced by lead nitrate (PbNO3), on FB1-induced cancer initiation. Initiation was effected over a period of 14 days by gavage administration of FB1 at different daily doses ranging from 0.14 to 3.5 mg FB1/100 g body weight while the stimuli for cell proliferation were introduced 7 days after the start of the FB1 treatment, Based on the proliferative stimulus used, cancer promotion was effected 3 weeks after completion of the initiating treatment by 2-acetylaminofluorene (2-AAF) treatment followed by PH or carbon tetrachloride CCl4 on day 4. Cancer initiation by FB1 was associated with a hepatotoxic effect and an increase in lipid peroxidation, In contrast to compensatory liver cell proliferation induced by PH and CCl4, mitogen-induced hyperplasia (PbNO3) failed to enhance the cancer initiating potential of FB1 suggesting that cancer induction by a non-genotoxic carcinogen is supported by regenerative cell proliferation. Cognizance of the enhancing role of cell proliferation during cancer initiation by FB1 is required in assessing the risks posed by this mycotoxin to humans. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.