Scholes E W, Basketter D A, Lovell W W, Sarll A E, Pendlington R U
Environmental Safety Laboratory, Unilever Research and Engineering, Sharnbrook, Bedford, United Kingdom.
Photodermatol Photoimmunol Photomed. 1991 Dec;8(6):249-54.
Guinea pig test methods are the most commonly used and reliable of predictive models for contact photoallergenicity of chemicals. The murine local lymph node assay (LLNA) has been developed recently as an alternative method for the identification of skin-sensitizing chemicals. Sensitization potential is measured from an assessment of the proliferation of lymphocytes in lymph nodes draining the site of exposure to the test chemical. This work investigates the activity of 6 widely reported photoactive chemicals in a modified LLNA (a photo-LLNA). The photoallergens tetrachlorosalicylanilide and fentichlor elicited positive ultraviolet radiation (UV)-dependent proliferative responses that were greater than their positive UV-independent responses, suggesting that they are both contact and photoallergic in the mouse. The lack of a proliferative response to 6-methylcoumarin and the absence of a reproducible response to musk ambrette suggest that the assay is insufficiently sensitive to identify weak photoallergic potential. Positive UV-dependent responses to acridine and anthracene, both photoirritants, cast doubt on the specificity of the photo-LLNA. Positive LLNA responses to these chemicals may be due to skin protein modification, based on evidence from the in vitro photo-chemical protein-binding assay. These results demonstrate that the photo-LLNA is able to detect at least moderate photoallergic potential.
豚鼠试验方法是预测化学物质接触性光致敏性最常用且可靠的模型。小鼠局部淋巴结试验(LLNA)是最近开发的一种用于鉴定皮肤致敏化学物质的替代方法。通过评估接触受试化学物质部位引流淋巴结中淋巴细胞的增殖来测定致敏潜力。这项工作研究了6种广泛报道的光活性化学物质在改良的LLNA(光LLNA)中的活性。光变应原四氯水杨酰苯胺和芬替克洛引发了阳性紫外线(UV)依赖性增殖反应,且大于其阳性非UV依赖性反应,这表明它们在小鼠中既是接触性又是光过敏性的。对6-甲基香豆素缺乏增殖反应以及对葵子麝香缺乏可重复反应表明该试验对鉴定弱光过敏潜力不够敏感。对吖啶和蒽这两种光刺激剂的阳性UV依赖性反应对光LLNA的特异性提出了质疑。基于体外光化学蛋白结合试验的证据表明,这些化学物质的阳性LLNA反应可能是由于皮肤蛋白质修饰。这些结果表明,光LLNA能够检测至少中等程度的光过敏潜力。