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

通过一系列动物实验证实了3-硝基苯甲酮(3-NBA)的急性毒性和致癌性。所有大鼠(F344/NSLC，雌性)在气管内注射3-NBA后6个月内死亡。这些大鼠表现出急性炎症，并伴有肺部化生改变。气管内给药后，大鼠(F344)无论雌雄均可诱发鳞状细胞癌，且呈剂量依赖关系。DNA加合物在肺中的含量最高，其次是肾脏和肝脏。可以检测到多达14种DNA加合物，其中四种主要的DNA加合物水平在总DNA加合物水平的50%-90%之间。肺、肾和肝脏的最大DNA加合物水平分别为240、180和35个DNA加合物/108个正常核苷酸(NN)。肺/肝和肾/肝之间的差异也有统计学意义(p&lt；0.05)，而肺和肾之间的差异不显著。尽管在线还原高效液相色谱-化学发光检测方法(R-HPLCCLD)对硝基…的检测更敏感当目标NPAC的环系中含有易被还原分解的反应性官能团或杂原子时，当目标NPAC的环系中含有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1000倍以上，这是因为除了相应的APAC之外，这种还原的f产物的形成导致CLD检测到的APAC分子的数量减少。此外，如果形成的非APAC产物的选择性不稳定依赖于NPAC的量，则将失去线性剂量响应。3-NBA就是其中一种带有反应性羰基的NPAC。因此，从灵敏度和准确性(响应和方差的线性)方面考察了R-HPC-CLD分析3-NBA的可行性。出乎意料的是，本研究采用的R-HPLC-CLD对3-NBA的灵敏度与1，8-DNP相当，检出限为20fmoL，定量下限为80fmoL，而1，8-DNP是最适合该方法的NPAc之一，在80-1500fmol范围内具有良好的线性关系，RSD为2.30/0。在本研究所采用的还原条件下，3-NBA到3-ABA的转化率估计为880/0。另一方面，所研究的7种NPAC对2-NTP的灵敏度不是很高(检测下限为40fmoL，定量下限为200fmoL)，但响应和RSD都很好。较少

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