Analysis of the mechanism of a defensive response newly found in skin epidermis to the mutagenic effect of UV.

我们发现了哺乳动物皮肤对UVB的一种生物学反应，即小鼠皮肤表皮的剂量依赖性突变诱导在高剂量范围内被抑制，我们称之为突变诱导抑制（MIS）。MIS反应被认为是一种组织特异性的生物反应，不能从细胞水平的体外研究中推断出来，并且可以通过基因组受损细胞的细胞排斥机制（如凋亡或免疫细胞杀伤）来介导。为了阐明MIS反应的机制，我们研究了皮肤表皮对UVB的凋亡和免疫炎症反应。然而，我们的组织学分析在方法学上并不成功。我们还对p53基因敲除小鼠进行了遗传分析，发现p53依赖的凋亡途径不会促进MIS反应。

We have found a biological response of mammalian skin to UVB that the dose-dependent mutation induction in mouse skin epidermis is suppressed at high dose range, the response that we call the mutation induction suppression (MIS). MIS response is thought to be a tissue-specific biological response that could not be deduced from cellular-level in vitro studies, and could be mediated through cell exclusion mechanisms of genomically damaged cells like apoptosis or immunological cell killing. To clarify the mechanism of MIS response, we studied the apoptotic and immunological inflammation responses in skin epidermis to UVB. However, our histological analyses have not been successful methodologically. We also performed a genetical analysis with a p53 gene-knockout mouse, and found that the p53-dependent apoptosis pathway would not contribute to MIS response.