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防晒霜对紫外线辐射诱导的小鼠黑色素瘤生长增强的影响。

Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice.

作者信息

Wolf P, Donawho C K, Kripke M L

机构信息

Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

出版信息

J Natl Cancer Inst. 1994 Jan 19;86(2):99-105. doi: 10.1093/jnci/86.2.99.

Abstract

BACKGROUND

Epidemiologic evidence suggests that exposure to UV radiation plays a significant role in the development of melanoma skin cancers. As early surgical removal of the melanoma is the only effective therapy, current strategies for reducing mortality from melanoma focus on prevention of the disease. Chemical sunscreens protect mice from development of skin cancers that resemble sunlight-induced human squamous cell cancers, but there appears to be a complex relationship between UV radiation exposure and development of melanoma.

PURPOSE

We asked whether common sunscreens would protect mice against UV radiation-induced enhancement of melanoma incidence.

METHODS

C3H mice were exposed to 4.8 kJ/m2 UVB from FS40 sunlamps twice a week for 3 weeks. Sunscreens containing 7.5% 2-ethylhexyl-p-methoxycinnamate, 8% octyl-N-dimethyl-p-aminobenzoate, 6% benzophenone-3, or the oil-in-water vehicle alone were applied to the ears and tails of the mice 20 minutes before irradiation. At various times during and after exposure, we determined UV radiation-induced inflammation by measuring ear swelling. We also examined the ears histologically for UV radiation-induced alterations. One day after the final irradiation, 2.5 x 10(4) syngeneic K1735 melanoma cells were injected into the external ears. Mice were examined weekly for tumor growth for 5-8 weeks after tumor cell injection. Control mice were treated in the identical way except for exposure to UV radiation.

RESULTS

The incidence of melanomas was significantly higher in the UV-irradiated mice. All three sunscreens protected against UV radiation-induced ear swelling and clearly diminished histopathologic alterations, including sunburn cell formation, epidermal hyperplasia, and mononuclear cell infiltrate in the dermis. However, the sunscreens failed to protect against UV radiation-induced increase in melanoma incidence. The sunscreens or vehicle alone did not significantly alter tumor growth.

CONCLUSIONS

Protection against sunburn does not necessarily imply protection against other possible UV radiation effects, such as enhanced melanoma growth.

IMPLICATIONS

Sunscreen protection against UV radiation-induced inflammation may encourage prolonged exposure to UV radiation and thus may actually increase the risk of melanoma development. These findings suggest that further research on the ability of sunscreens to prevent melanoma is urgently needed.

摘要

背景

流行病学证据表明,暴露于紫外线辐射在皮肤黑色素瘤的发生发展中起重要作用。由于早期手术切除黑色素瘤是唯一有效的治疗方法,目前降低黑色素瘤死亡率的策略主要集中在疾病预防上。化学防晒剂可保护小鼠免受类似于阳光诱导的人类鳞状细胞癌的皮肤癌的侵害,但紫外线辐射暴露与黑色素瘤的发生之间似乎存在复杂的关系。

目的

我们探讨了常用防晒剂是否能保护小鼠免受紫外线辐射诱导的黑色素瘤发病率增加的影响。

方法

将C3H小鼠每周两次暴露于FS40太阳灯下4.8 kJ/m2的UVB辐射,持续3周。在照射前20分钟,将含有7.5% 2-乙基己基对甲氧基肉桂酸酯、8%辛基-N-二甲基对氨基苯甲酸酯、6%二苯甲酮-3的防晒剂或单独的水包油载体涂抹于小鼠的耳朵和尾巴上。在暴露期间及之后的不同时间,通过测量耳朵肿胀来确定紫外线辐射诱导的炎症。我们还对耳朵进行组织学检查,以观察紫外线辐射引起的改变。在最后一次照射后一天,将2.5×10(4)个同基因K1735黑色素瘤细胞注射到外耳中。在肿瘤细胞注射后5至8周,每周检查小鼠的肿瘤生长情况。对照小鼠除不接受紫外线辐射外,采用相同的方法处理。

结果

紫外线照射小鼠的黑色素瘤发病率显著更高。所有三种防晒剂均能防止紫外线辐射引起的耳朵肿胀,并明显减轻组织病理学改变,包括晒伤细胞形成、表皮增生和真皮单核细胞浸润。然而,这些防晒剂未能防止紫外线辐射引起的黑色素瘤发病率增加。单独使用防晒剂或载体对肿瘤生长没有显著影响。

结论

防止晒伤并不一定意味着能防止紫外线辐射的其他可能影响,如黑色素瘤生长增强。

启示

防晒剂对紫外线辐射诱导的炎症的防护作用可能会鼓励人们延长紫外线辐射暴露时间,从而实际上可能增加黑色素瘤发生的风险。这些发现表明,迫切需要进一步研究防晒剂预防黑色素瘤的能力。

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