一项研究发现，咖啡因看上去能够在分子层次上预防某些皮肤癌，该研究解释了这个过程的可能运作机制。Masaoki Kawasumi及其同事对小鼠进行了遗传改造从而减少了共济失调毛细血管扩张症和Rad3相关酶（称为ATR）在其皮肤中的功能。
此前的研究表明，咖啡因抑制了ATR，反过来促进了DNA受损的细胞的死亡。当接触紫外线的时候，经过遗传改造的小鼠比未经改造的小鼠的肿瘤晚出现了3周。在接触紫外线19周之后，经过改造的小鼠比普通小鼠的肿瘤少69%，而且浸润性肿瘤是后者的1/4。然而， 在接触紫外线34周后，持续的长期紫外线照射最终导致了所有这些小鼠出现肿瘤。
这些发现提示，其他研究发现的咖啡因具防止紫外线破坏的作用很可能是由于在紫外线诱导的皮肤癌全面发展之前的前癌阶段ATR被抑制。这组科研人员提出，局部使用咖啡因可能有助于预防这类癌症，再加上它还能直接吸收紫外线，因此它可以作为一种防晒剂。
生物探索推荐英文论文摘要：
Protection from UV-induced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase
Abstract
Multiple human epidemiologic studies link caffeinated (but not decaffeinated) beverage intake with significant decreases in several types of cancer, including highly prevalent UV-associated skin carcinomas. The mechanism by which caffeine protects against skin cancer is unknown. Ataxia telangiectasia and Rad3-related (ATR) is a replication checkpoint kinase activated by DNA stresses and is one of several targets of caffeine. Suppression of ATR, or its downstream target checkpoint kinase 1 (Chk1), selectively sensitizes DNA-damaged and malignant cells to apoptosis. Agents that target this pathway are currently in clinical trials. Conversely, inhibition of other DNA damage response pathways, such as ataxia telangiectasia mutated (ATM) and BRCA1, promotes cancer. To determine the effect of replication checkpoint inhibition on carcinogenesis, we generated transgenic mice with diminished ATR function in skin and crossed them into a UV-sensitive background, Xpc−/−. Unlike caffeine, this genetic approach was selective and had no effect on ATM activation. These transgenic mice were viable and showed no histological abnormalities in skin. Primary keratinocytes from these mice had diminished UV-induced Chk1 phosphorylation and twofold augmentation of apoptosis after UV exposure (P = 0.006). With chronic UV treatment, transgenic mice remained tumor-free for significantly longer (P = 0.003) and had 69% fewer tumors at the end of observation of the full cohort (P = 0.019), compared with littermate controls with the same genetic background. This study suggests that inhibition of replication checkpoint function can suppress skin carcinogenesis and supports ATR inhibition as the relevant mechanism for the protective effect of caffeinated beverage intake in human epidemiologic studies.
