Mantle Peter
Centre for Environmental Policy, Imperial College London, London SW7 2AZ, UK.
J Kidney Cancer VHL. 2016 Sep 26;3(3):1-10. doi: 10.15586/jkcvhl.2016.58. eCollection 2016.
An experiment to explore renal carcinogenic efficacy of male rat exposure to dietary ochratoxin A (OTA) only in the first year of life has been made in comparison to lifetime exposure. Ten months exposure to OTA at 300 µg/kg b.w. was sufficient to cause high incidence of tumours which became apparent clinically after a latency of up to a year. As a putative model for human kidney cancer, the study shows a silent organ-specific carcinogenic effect through protracted exposure up to middle age and focused probably on very few nephrons. So far, tumourigenesis has not been recognised until in the last quarter of natural rat life, but for OTA, rat renal carcinogenesis requires both long exposure and only during the first year of normal longevity. The present findings offer an experimental framework within which systematic histopathology during tumourigenesis might show whether findings of mechanistic studies in key focal neoplasms can reasonably be applied to OTA as a putative renal carcinogen for idiopathic kidney cancer in humans. Already, the rat tumours mimic those occurring spontaneously in the Eker rat, and there is disparity between the large necessary OTA exposure in the rat and the trace amounts of OTA consumed by humans. In all such complex considerations it is important to adhere rigorously to established principles of disease epidemiology.
开展了一项实验，将雄性大鼠仅在生命的第一年暴露于膳食中的赭曲霉毒素A（OTA）的肾脏致癌效果与终生暴露的情况进行比较。以300 µg/kg体重的剂量暴露于OTA十个月就足以导致高肿瘤发生率，这些肿瘤在长达一年的潜伏期后在临床上变得明显。作为人类肾癌的一种假定模型，该研究显示了通过持续暴露至中年而产生的一种隐匿的器官特异性致癌作用，且可能集中在极少数肾单位上。到目前为止，直到大鼠自然寿命的最后一个季度才识别出肿瘤发生，但对于OTA而言，大鼠肾脏致癌作用既需要长期暴露，且仅在正常寿命的第一年期间。目前的研究结果提供了一个实验框架，在该框架内，肿瘤发生过程中的系统组织病理学可能会表明，关键局灶性肿瘤的机制研究结果是否能够合理地应用于OTA，将其作为人类特发性肾癌的一种假定肾致癌物。大鼠肿瘤已经类似于Eker大鼠中自发发生的肿瘤，并且大鼠中所需的大量OTA暴露与人类摄入的痕量OTA之间存在差异。在所有这些复杂的考量中，严格遵循既定的疾病流行病学原则非常重要。
