Evaluation of the formation process and the biological effects of 3-nitrobenzanthrone, a strong mutagen newly identified from particulate matter in urban air.

评估3-硝基苯并蒽酮的形成过程和生物效应，这是一种新从城市空气颗粒物中鉴定出的强诱变剂。

• 批准号: 14380259
• 负责人: ADACHI Shuichi
• 金额: $ 7.94万
• 依托单位: Sagami Women's University (2003-2004)National Institute of Public Health (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14380259/
• 关键词: Nitrobenzanthrone; Nitroarene; DNA adduct; Diesel; Lung tumor; Lung cancer; Mutagenicity; Air pollution; ニトロアーレン; 変異原物質; 発癌物質

Acute toxicity and carcinogenicity of 3-nitrobenzanthrone (3-NBA) were demonstrated by a series of animal experiments. All rats (F344/Nslc, female) had died within 6 months after the intratracheal administration of 3-NBA. These rats showed acute inflammation with metaplastic changes in the lung. Squamous cell carcinomas were induced dose dependently in both sex of rats (F344) after intratracheal administration. The highest level of DNA adducts was found in the lung, followed by the kidney and the liver. Up to 14 DNA adducts could be detected with four major ones varying between 50-90% of the total DNA adduct level. The maximum levels of DNA adducts were on average 240, 180 and 35 DNA adducts/10^8 normal nucleotides (NN) for lung, kidney and liver, respectively. There was also a significant difference (p <0.05) between lung/liver and kidney/liver but not between lung and kidney.Although on-line reduction HPLC with chemiluminescence detection (R-HPLC-CLD) are much more sensitive to nitro … More arenes such as nitropyrenes up to by a factor of 1000 than conventional GC-MS system, the specific sensitivity would decrease when target NPAC have reactive functional groups or heteroatoms in the ring system, which are easy to be reductively decomposed, since formation of such reduced f products other than corresponding APAC results a decrease in the number of the APAC molecule detected by CLD. Moreover, if non APAC products are formed with unstable selectivity depending on the amount of NPAC, linear dose-response will be lost. 3-NBA is one of such NPAC with reactive carbonyl group. Thus feasibility of 3-NBA analysis by R-HPC-CLD was examined in sensitivity and accuracy (linearity of the response and variance). Unexpectedly, R-HPLC-CLD employed in this study exhibited quite high sensitivity to 3-NBA (20 fmol for detection limit and 80 fmol for quantification limit) comparable to 1,8-DNP, which is one of the most suitable NPAC for this method, and excellent linear response between 80-1500 fmol with RSD of 2.30/0. The conversion of 3-NBA to 3-ABA was estimated to be 880/0 under the reduction condition employed in this study. On the other hand, the sensitivity to 2-NTP was not so high among seven NPAC investigated (40 fmol for detection limit and 200 fmol for quantification limit) while linearity of the response and RSD were excellent. Less

通过一系列动物实验证实了3-硝基苯蒽酮（3-NBA）的急性毒性和致癌性。所有大鼠（F344/Nslc，雌性）均在3-NBA内给药后6个月内死亡。这些大鼠表现出急性炎症伴肺化生变化。经阴道给药后，在两种性别的大鼠（F344）中均以剂量依赖性方式诱导鳞状细胞癌。DNA加合物的最高水平被发现在肺，其次是肾脏和肝脏。最多可检测到14种DNA加合物，其中4种主要加合物占总DNA加合物水平的50-90%。肺、肾和肝中DNA加合物的最大水平平均分别为240、180和35 DNA加合物/10^8正常核苷酸（NN）。虽然在线还原高效液相色谱化学发光检测法（R-HPLC-CLD）对硝基甲苯的检测灵敏度较高，但在肺/肝和肾/肝之间有显著性差异（p <0.05），而在肺/肾之间无显著性差异（p> 0.05） ...更多信息 芳烃，如硝基芘，比常规GC-MS系统高1000倍，当目标NPAC在环系统中具有容易被还原分解的反应性官能团或杂原子时，比灵敏度会降低，因为形成这种还原产物而不是相应的APAC导致CLD检测到的APAC分子数量减少。此外，如果形成的非APAC产物具有取决于NPAC量的不稳定选择性，则将失去线性剂量响应。3-NBA是一种具有反应性羰基的NPAC。因此，从灵敏度和准确度（响应和方差的线性）方面检查了R-HPC-CLD进行3-NBA分析的可行性。出乎意料的是，本研究中使用的R-HPLC-CLD对3-NBA表现出相当高的灵敏度（检测限为20 fmol，定量限为80 fmol），与1，8-DNP相当，这是该方法最合适的NPAC之一，并且在80-1500 fmol之间具有优异的线性响应，RSD为2.30/0.05。在本研究所用的还原条件下，3-NBA转化为3-阿坝的转化率估计为880/0。另一方面，在所研究的7种NPAC中，对2-NTP的灵敏度不太高（检测限为40 fmol，定量限为200 fmol），而响应的线性和RSD均良好。少