Uno Yoshifumi, Morita Takeshi, Luijten Mirjam, Beevers Carol, Hamada Shuichi, Itoh Satoru, Ohyama Wakako, Takasawa Hironao
Mitsubishi Tanabe Pharma Co., Chiba, Japan.
National Institute of Health Sciences, Tokyo, Japan.
Mutat Res Genet Toxicol Environ Mutagen. 2015 May 1;783:19-22. doi: 10.1016/j.mrgentox.2015.03.001. Epub 2015 Mar 5.
At the 6th International Workshop on Genotoxicity Testing, the liver micronucleus test (MNT) working group briefly discussed the MNT using tissues other than liver/erythrocytes. Many tissues other than liver/erythrocytes have been studied, primarily for research purposes. They have included the colon and intestinal epithelium, skin, spleen, lung, stomach, bladder, buccal mucosa, vagina, and fetal/neonatal tissues. These tissues were chosen because they were target sites of carcinogens, and/or relevant to a specific route of exposure. Recently, there has been particular focus on the gastrointestinal (GI) tract as it is a contact site associated with high exposure following oral gavage. Furthermore GI tumors are observed with high frequency in human populations. A collaborative study of the rat glandular stomach and colon MNT was conducted in conjunction with a collaborative study of the repeated-dose liver MNT. Based on limited data currently available, the rodent MNT using the glandular stomach and/or colon seems to detect genotoxic carcinogens with GI tract target-organ specificity. The working group concluded that the GI tract MNT would be a promising method to examine clastogenicity or aneugenicity of test chemicals in the stomach and/or colon. Further data will be needed to fully establish the methods, and to identify the sensitivity and specificity of the GI tract MNT.
在第六届遗传毒性检测国际研讨会上,肝脏微核试验(MNT)工作组简要讨论了使用肝脏/红细胞以外组织的MNT。除肝脏/红细胞外,许多组织已被研究,主要用于研究目的。这些组织包括结肠和肠上皮、皮肤、脾脏、肺、胃、膀胱、颊黏膜、阴道以及胎儿/新生儿组织。选择这些组织是因为它们是致癌物的靶位点,和/或与特定暴露途径相关。最近,胃肠道(GI)受到了特别关注,因为它是经口灌胃后高暴露相关的接触部位。此外,胃肠道肿瘤在人群中观察到的频率很高。大鼠腺胃和结肠MNT的合作研究与重复剂量肝脏MNT的合作研究同时进行。根据目前有限的数据,使用腺胃和/或结肠的啮齿动物MNT似乎能检测出对胃肠道具有靶器官特异性的遗传毒性致癌物。工作组得出结论,胃肠道MNT将是一种有前景的方法,用于检测受试化学物质在胃和/或结肠中的致断裂性或致非整倍体性。需要更多数据来全面确立这些方法,并确定胃肠道MNT的敏感性和特异性。