Yokohira Masanao, Hashimoto Nozomi, Yamakawa Keiko, Suzuki Satoshi, Saoo Kousuke, Kuno Toshiya, Imaida Katsumi
Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
J Toxicol Pathol. 2009 Mar;22(1):71-8. doi: 10.1293/tox.22.71. Epub 2009 Apr 6.
Toxicity assessment of nanoparticles, now widespread in our environment, is an important issue. We have focused attention on the carcinogenic potential of copper oxide (CuO) and titanium dioxide (TiO(2)). In experiment 1, a sequential pilot study, the effectiveness of a carcinogenic bioassay featuring intraperitoneal injection (i.p.) of 20 mg 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or 0.1% N-bis(2-hydroxypropyl)nitrosamine (DHPN) in drinking water for 2 weeks was examined. Based on the results, DHPN, as the lung carcinogen, and evaluation at week 30 were selected as the most appropriate for our purposes in Experiment 1. In experiment 2, the carcinogenic bioassay was used to assess the carcinogenic potentials of instilled nanoparticles of CuO and TiO(2). There were no significant intergroup differences in the lung neoplastic lesions induced by DHPN, although the neoplastic lesions induced by the nanoparticles in the CuO or TiO(2) intratracheal instillation (i.t.) groups, demonstrated a tendency to increase compared with the microparticles administration. At the very least, the carcinogenic bioassay with DHPN proved useful for assessment of the modifying effects of instilled particles, and further assessment of the carcinogenic potential of nanoparticles appears warranted.
纳米颗粒如今在我们的环境中广泛存在，对其毒性评估是一个重要问题。我们将重点关注氧化铜（CuO）和二氧化钛（TiO₂）的致癌潜力。在实验1中，这是一项序贯性预试验，研究了腹腔注射20毫克4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）或在饮用水中添加0.1% N-双（2-羟丙基）亚硝胺（DHPN）持续2周的致癌生物测定法的有效性。基于这些结果，DHPN作为肺致癌物以及在第30周进行评估被选为最适合我们在实验1中的目的。在实验2中，致癌生物测定法被用于评估经气管滴注的CuO和TiO₂纳米颗粒的致癌潜力。尽管与给予微粒相比，CuO或TiO₂气管内滴注（i.t.）组中纳米颗粒诱导的肿瘤性病变有增加的趋势，但DHPN诱导的肺肿瘤性病变在组间没有显著差异。至少，用DHPN进行的致癌生物测定法被证明可用于评估滴注颗粒的修饰作用，并且对纳米颗粒致癌潜力的进一步评估似乎是有必要的。
