Papanikolaou A, Wang Q S, Delker D A, Rosenberg D W
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs 06269-2092, USA.
Cancer Lett. 1998 Aug 14;130(1-2):29-34. doi: 10.1016/s0304-3835(98)00101-3.
Azoxymethane (AOM) is an organotropic colon carcinogen that is commonly used to induce colon tumors in rodents. Unlike its parent compound, 1,2-dimethylhydrazine (DMH), a tumor susceptibility phenotype in inbred mice with respect to AOM has not been established. Thus, this study was undertaken to determine whether genetic susceptibility extends to this carcinogen. SWR/J, A/J (both susceptible to DMH carcinogenesis) and AKR/J (resistant) mice were treated with 10 mg/kg AOM i.p. once a week for 8 weeks. Twenty-five weeks after the initial injection, tumor yield was determined. With a single exception, only SWR/J and A/J mice developed tumors, with a distribution that was limited to the distal colon (16.3+/-1.1 and 36.4+/-2.4. respectively). The formation of aberrant crypt foci (ACF), putative preneoplastic lesions, was also assessed in whole-mount colons using Methylene Blue staining. Consistent with tumor multiplicity, the total number of ACF was highest in A/J mice, followed by SWR/J mice. In addition, A/J mice had a significantly greater number of large ACF (five or more crypts per foci) than the other strains. Despite the absence of colon tumors, however, AKR/J mice did develop a significant number of ACF. This finding suggests that ACF in resistant mice are persistent but do not progress to tumors.
偶氮甲烷（AOM）是一种亲器官性结肠致癌物，常用于诱导啮齿动物发生结肠肿瘤。与其母体化合物1,2 - 二甲基肼（DMH）不同，关于AOM在近交系小鼠中的肿瘤易感性表型尚未确定。因此，本研究旨在确定遗传易感性是否也适用于这种致癌物。将SWR/J、A/J（两者均对DMH致癌作用敏感）和AKR/J（抗性）小鼠腹腔注射10 mg/kg AOM，每周一次，共8周。初次注射后25周，测定肿瘤发生率。除了一个例外，只有SWR/J和A/J小鼠发生了肿瘤，且分布仅限于远端结肠（分别为16.3±1.1和36.4±2.4）。还使用亚甲蓝染色对整个结肠进行评估，以确定异常隐窝灶（ACF）（假定的癌前病变）的形成情况。与肿瘤多发性一致，A/J小鼠中ACF的总数最高，其次是SWR/J小鼠。此外，A/J小鼠中大型ACF（每个病灶有五个或更多隐窝）的数量明显多于其他品系。然而，尽管AKR/J小鼠没有发生结肠肿瘤，但确实出现了大量的ACF。这一发现表明，抗性小鼠中的ACF持续存在，但不会发展为肿瘤。
