UAB Department of Genetics, Birmingham, AL 35294, USA.
Vet Pathol. 2011 Mar;48(2):420-6. doi: 10.1177/0300985810377183. Epub 2010 Aug 17.
The authors recently assessed the likelihood that lifetime cancer bioassays of aspartame, methanol, and methyl tertiary butyl ether conducted with conventional (not specific pathogen free) Sprague-Dawley rats were compromised by Mycoplasma pulmonis disease. From the tumor data and other information, the authors concluded that the rats used in these bioassays likely had M pulmonis disease and that lesions of the disease were plausibly interpreted as lymphoma. Subsequently, they analyzed the nonneoplastic lesion data from these bioassays for occurrence of inflammatory lesions and found that 2,267 of 2,960 rats (76.6%) were reported to have bronchitis, the signature lesion of M pulmonis disease, and that 633 rats (21.4%) were reported to have otitis, another common lesion of the disease. Also, documentation is now available containing serologic evidence of mycoplasma infection in the rats. In contrast, the reports of 6 National Toxicology Program bioassays based on specific pathogen-free Sprague-Dawley rats listed no instances of bronchitis or otitis. These findings provide substantial additional evidence that the bioassays in question were compromised by M pulmonis disease. Therefore, the reported induction of lymphoma in these studies should not be considered in cancer risk assessments. The authors also found that inflammatory lesions were prevalent in lymph nodes, thymus, pleura, and brain. Finally, they found that of all 328 cases of lymphoimmunoblastic lymphoma affecting the lung (the primary form of lymphoma reported), 218 (66.5%) occurred within the first 104 weeks of the studies, showing that occurrence of such lesions was not due to appearance in rats surviving beyond that interval.
作者最近评估了使用常规（非无特定病原体）Sprague-Dawley 大鼠进行阿斯巴甜、甲醇和甲基叔丁基醚终生癌症生物测定的可能性，这些生物测定是否受到支原体肺炎疾病的影响。从肿瘤数据和其他信息来看，作者得出结论，这些生物测定中使用的大鼠可能患有支原体肺炎疾病，并且疾病的病变很可能被解释为淋巴瘤。随后，他们分析了这些生物测定中非肿瘤病变数据中炎症病变的发生情况，发现 2960 只大鼠中有 2267 只（76.6%）报告患有支气管炎，这是支原体肺炎疾病的标志性病变，并且有 633 只大鼠（21.4%）报告患有中耳炎，这是该疾病的另一种常见病变。此外，现在有文件证明大鼠存在支原体感染的血清学证据。相比之下，6 项基于无特定病原体 Sprague-Dawley 大鼠的国家毒理学计划生物测定报告中没有支气管炎或中耳炎的病例。这些发现提供了大量额外的证据，表明所讨论的生物测定受到支原体肺炎疾病的影响。因此，不应在癌症风险评估中考虑这些研究中报告的淋巴瘤诱导。作者还发现，炎症病变在淋巴结、胸腺、胸膜和大脑中很普遍。最后，他们发现，所有 328 例肺淋巴免疫母细胞性淋巴瘤（报告的主要淋巴瘤形式）中，有 218 例（66.5%）发生在研究的前 104 周内，表明此类病变的发生并非由于在该间隔后存活的大鼠中出现。
