ToxPath Inc., 3028 Ethan Lane, Raleigh, NC 27613, USA.
Regul Toxicol Pharmacol. 2010 Mar;56(2):166-73. doi: 10.1016/j.yrtph.2009.12.007. Epub 2010 Jan 4.
This companion article offers an alternative interpretation for the quinacrine-induced uterine tumors observed in a 2-year bioassay in rats (CaBio, Cancel et al., 2010), and provides additional data from two new experiments that support a different interpretation and analysis. Our major premise is that the design of the Cancel et al. bioassay was flawed, particularly regarding dose selection that allowed for misinterpretation of carcinogenic activity. We feel the totality of the information provided herein dictates that the doses (70/70, 70/250 and 70/350 mg/kg quinacrine) causing uterine tumors in their study clearly exceeded the maximum tolerated dose (MTD) typically administered in chronic cancer studies. Our new data support this conclusion and serve to explain the development of lesions, especially the uterine tumors, they have reported. We argue that the rat uterus is not a valid surrogate for the human fallopian tube. Further, we maintain that quinacrine is not genotoxic in vivo, as suggested in their paper. In summary, we believe that quinacrine is not carcinogenic in rats at doses that do not exceed the MTD.
这篇伴随文章为喹吖因诱导的大鼠 2 年生物测定中观察到的子宫肿瘤提供了另一种解释（CaBio，Cancel 等人，2010 年），并提供了两个新实验的额外数据，这些数据支持了不同的解释和分析。我们的主要前提是，Cancel 等人的生物测定设计存在缺陷，特别是在允许对致癌活性产生误解的剂量选择方面。我们认为，本文提供的全部信息表明，导致其研究中子宫肿瘤的剂量（70/70、70/250 和 70/350mg/kg 喹吖因）明显超过了慢性癌症研究中通常给予的最大耐受剂量（MTD）。我们的新数据支持这一结论，并有助于解释他们所报告的病变的发展，特别是子宫肿瘤。我们认为，大鼠子宫不是人类输卵管的有效替代物。此外，我们认为喹吖因在体内没有遗传毒性，正如他们在论文中所指出的。总之，我们认为喹吖因在不超过 MTD 的剂量下对大鼠没有致癌性。
