Sherwani Mohammed Asif, Burns Erin M, Ahmad Israr, Jasser Ahmed Omar, Chandra Ariq, Yusuf Nabiha
Department of Dermatology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Nutrients. 2024 Dec 13;16(24):4314. doi: 10.3390/nu16244314.
BACKGROUND/OBJECTIVE: Ultraviolet (UV) B radiation leads to DNA damage by generating cyclobutane pyrimidine dimers (CPDs). UVB-induced CPDs can also result in immune suppression, which is a major risk factor for non-melanoma skin cancer (NMSC). UVB-induced CPDs are repaired by nucleotide repair mechanisms (NER) mediated by xeroderma pigmentosum complementation group A (XPA). The purpose of this study was to investigate the use of TH as a chemopreventive agent against the development of skin cancer.
SKH-1 hairless mice were exposed were fed with TH (0.1% /) for two weeks and exposed to a single dose of UVB (180 mJ/cm). Dorsal skin was harvested 24 h post-UVB exposure for evaluation of DNA damage and repair. Lymph nodes were also harvested to prepare single cell suspension for flow cytometric evaluation. For carcinogenesis experiments, SKH-1 hairless mice were given TH (0.1% /) ad libitum and exposed to UVB (180 mJ/cm) thrice a week for 30 weeks.
Feeding SKH-1 hairless mice with TH (0.1% /) for two weeks prior to a single dose of UVB (180 mJ/cm) led to a significant increase in XPA in skin and DNA repair cytokines IL-12 and IL-23 in draining lymph nodes. Furthermore, when subjected to the photocarcinogenesis protocol; mice fed with TH developed significantly fewer tumors in comparison to mice fed on drinking water.
Our data demonstrate that TH has a protective effect against UVB-induced DNA damage, immune suppression, and skin cancer. Future studies will further investigate the potential of TH as a preventive treatment for NMSC.
背景/目的:紫外线B(UVB)辐射通过产生环丁烷嘧啶二聚体(CPD)导致DNA损伤。UVB诱导的CPD也可导致免疫抑制,这是非黑色素瘤皮肤癌(NMSC)的主要危险因素。UVB诱导的CPD由着色性干皮病互补组A(XPA)介导的核苷酸修复机制(NER)修复。本研究的目的是调查TH作为皮肤癌化学预防剂的用途。
将SKH-1无毛小鼠喂食TH(0.1%/)两周,然后暴露于单剂量UVB(180 mJ/cm²)。在UVB暴露后24小时采集背部皮肤,用于评估DNA损伤和修复。还采集淋巴结以制备单细胞悬液用于流式细胞术评估。对于致癌实验,给予SKH-1无毛小鼠自由摄取TH(0.1%/),并每周三次暴露于UVB(180 mJ/cm²),持续30周。
在单剂量UVB(180 mJ/cm²)照射前两周,给SKH-1无毛小鼠喂食TH(0.1%/)导致皮肤中XPA以及引流淋巴结中DNA修复细胞因子IL-12和IL-23显著增加。此外,在进行光致癌方案时,与饮用自来水的小鼠相比,喂食TH的小鼠发生的肿瘤明显更少。
我们的数据表明,TH对UVB诱导的DNA损伤、免疫抑制和皮肤癌具有保护作用。未来的研究将进一步调查TH作为NMSC预防性治疗的潜力。