F. Hoffmann-La Roche Ltd., Non Clinical Safety, B. 073/215A, Ch-4070 Basel, Switzerland.
Mutat Res. 2011 Aug 16;723(2):129-33. doi: 10.1016/j.mrgentox.2011.03.017. Epub 2011 Apr 29.
The polycyclic aromatic hydrocarbon azulene and its naturally occurring derivative guaiazulene (1,4-dimethyl-7-isopropylazulene) are known to absorb light in the UV-vis region of the spectrum. Both compounds were reported to be mutagenic in the Salmonella typhimurium bacterial mutagenicity assay (Ames test) in strain TA102, and to cause DNA damage in the comet assay in vitro upon exposure to UVA light. In contrast, another study reported a photoprotective effect in vitro of guaiazulene. We present here a comprehensive assessment of the photo(cyto)toxicity (3T3 fibroblast Neutral Red uptake test), the photomutagenicity (Ames test) and photogenotoxicity (comet assay and micronucleus test in L5178Y cells in vitro) of azulene. In the Ames test, the mutagenicity of azulene was assessed in the presence and absence of UV light by use of the Salmonella strains TA102, TA104, TA2638 and E. coli WP2. Azulene was irradiated before being plated with bacteria (pre-irradiation), or concomitantly with the bacteria either after plating or while in suspension. Guaiazulene was included in some of the experiments. Neither in the photo-Ames test nor in the other photogenotoxicity tests, azulene or guaiazulene showed any photomutagenic or photogenotoxic activity. Weak photo(cyto)toxicity (estimate of PIF≥1.67) was observed with azulene in the 3T3 NRU test, the Alamar Blue test and the relative cell count, which may be due to the generation of reactive oxygen species, as reported recently.
多环芳烃蓝烯及其天然衍生物愈创木薁（1,4-二甲基-7-异丙基薁）已知在光谱的紫外可见区域吸收光。这两种化合物都被报道在沙门氏菌伤寒突变测试（Ames 测试）中在 TA102 菌株中具有致突变性，并在体外 UVA 光照射下在彗星试验中引起 DNA 损伤。相比之下，另一项研究报告了愈创木薁在体外的光保护作用。我们在这里全面评估了蓝烯的光（细胞）毒性（3T3 成纤维细胞中性红摄取试验）、光致突变性（Ames 测试）和光遗传毒性（彗星试验和 L5178Y 细胞微核试验）。在 Ames 测试中，通过使用沙门氏菌菌株 TA102、TA104、TA2638 和 E. coli WP2，在存在和不存在紫外光的情况下评估了蓝烯的致突变性。在与细菌共培养之前（预辐照）或在与细菌共培养时（共培养后）或在悬浮液中辐照蓝烯。在一些实验中包括了愈创木薁。在光-Ames 测试和其他光遗传毒性测试中，蓝烯或愈创木薁均未显示出任何光致突变或光遗传毒性活性。在 3T3 NRU 试验、Alamar Blue 试验和相对细胞计数中观察到蓝烯具有弱的光（细胞）毒性（估计的 PIF≥1.67），这可能是由于最近报道的活性氧的产生所致。
