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一种用于研究局部光过敏的预测性小鼠耳肿胀模型。

A predictive mouse ear-swelling model for investigating topical photoallergy.

作者信息

Gerberick G F, Ryan C A

机构信息

Procter & Gamble Co., Miami Valley Laboratories, Cincinnati, OH 45239-8707.

出版信息

Food Chem Toxicol. 1990 May;28(5):361-8. doi: 10.1016/0278-6915(90)90110-9.

Abstract

The photoallergic potential of various compounds was assessed using a mouse ear-swelling model, which offers the advantage of being quantifiable and more objective than models based on subjective evaluation of erythematous skin reactions. Cyclophosphamide pretreated BALB/c mice were induced by topical treatment of the dorsal skin surface on 3 consecutive days and challenged on the ears 5 days after the last induction. For each induction and challenge treatment, mice were consecutively irradiated with ultraviolet (UV) A (10 J/cm2) and UVB (45 mJ/cm2) radiation 30 min to 1 hr after test material application. The photoallergic response to musk ambrette, a known human photoallergen, was significantly augmented when three consecutive induction exposures were used as compared with one or two inductions. The photoallergic potential of nine other known human photoallergens (tetrachlorosalicylanilide, bithionol, 6-methylcoumarin, chlorpromazine, sodium omadine, bisphenol A, sulphanilamide, fentichlor and p-aminobenzoic acid) was successfully detected using the mouse model. In each experiment, the ear thickness changes observed in the photoallergy test mice were significantly greater than the changes observed in the contact allergy, vehicle/radiation and phototoxicity control mice. Coumarin and homosalate, two agents not traditionally associated with causing photoallergy in humans or animals, did not demonstrate contact photoallergy using this model. With three of the photoallergens, musk ambrette, bithionol and tetrachlorosalicylanilide, the ear swelling response obtained was due to photoallergy alone and not due to the co-existence of both contact photoallergy and contact allergy. In addition, irradiating mice 24 hr, rather than 1 hr, following application of the test material during the induction phase resulted in a significantly reduced photoallergic response with both musk ambrette and tetrachlorosalicylanilide. These results indicate that the mouse ear-swelling model is a potentially useful model for investigative and predictive photoallergy testing.

摘要

使用小鼠耳部肿胀模型评估了各种化合物的光过敏潜力,该模型具有可量化的优势,且比基于对皮肤红斑反应进行主观评估的模型更客观。对环磷酰胺预处理的BALB/c小鼠连续3天进行背部皮肤表面局部处理以诱导反应,并在最后一次诱导后5天对耳部进行激发。对于每次诱导和激发处理,在涂抹测试材料后30分钟至1小时,小鼠依次接受紫外线A(10 J/cm²)和紫外线B(45 mJ/cm²)照射。与一次或两次诱导相比,当使用连续三次诱导暴露时,对已知的人类光变应原葵子麝香的光过敏反应显著增强。使用该小鼠模型成功检测了其他九种已知的人类光变应原(四氯水杨酰苯胺、硫双二氯酚、6-甲基香豆素、氯丙嗪、奥麦丁钠、双酚A、磺胺、芬替克洛和对氨基苯甲酸)的光过敏潜力。在每个实验中,光过敏测试小鼠耳部厚度的变化显著大于接触过敏、赋形剂/辐射和光毒性对照小鼠中观察到的变化。香豆素和胡莫柳酯这两种传统上与人类或动物光过敏无关的物质,使用该模型未表现出接触性光过敏。对于三种光变应原葵子麝香、硫双二氯酚和四氯水杨酰苯胺,获得的耳部肿胀反应仅归因于光过敏,而非接触性光过敏和接触过敏同时存在。此外,在诱导阶段涂抹测试材料后24小时而非1小时照射小鼠,会使葵子麝香和四氯水杨酰苯胺的光过敏反应显著降低。这些结果表明,小鼠耳部肿胀模型是用于研究性和预测性光过敏测试的潜在有用模型。

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