Epidermal proliferation but not the quantity of DNA photodamage is correlated with UV-induced mouse skin carcinogenesis
Epidermal proliferation but not the quantity of DNA photodamage is correlated with UV-induced mouse skin carcinogenesis
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DOI：
10.1111/1523-1747.ep12335984
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发表时间：
1997-09-01
影响因子：
6.5
通讯作者：
Locniskar, MF
中科院分区：
文献类型：
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作者：
Berton, TR;Mitchell, DL;Locniskar, MF
与Sencar品系相比，无毛SKH-1小鼠品系具有更高的皮肤肿瘤发病率、更短的肿瘤潜伏期和更高的肿瘤产量。在这项研究中，我们通过测量一次UV处理后和慢性UV照射1、3、6和9wk后两个菌株的DNA光损伤和表皮增殖来评估两个菌株对紫外线敏感性的差异，SKH-1菌株对环丁烷嘧啶二聚体(CPDS)和嘧啶(6-4)嘧啶二聚体((6-4)PDs)的诱导率显著高于Sencar菌株，但对CPDS和(6-4)PDs的修复动力学没有检测到菌株差异，在慢性UV照射下，我们观察到：(I)两个菌株的DNA光损伤程度相同；(2)6周后(6-4个)PDs数量显著多于CPDS：(3)SKH-1株表皮细胞数显著增加(1.5倍)；(4)5-溴-2‘-脱氧尿嘧啶核苷(BrdU)测定的周期细胞数位于基底和基底上，SKH-1株显著多于SKH-1株；而SKH-1株在紫外线照射9wk后，P53免疫反应阳性的细胞数相当，而SKH-1株的阳性细胞位于基底以上。这些结果表明，紫外线在肿瘤发生中的致病作用与小鼠表皮DNA光损伤量以外的事件有关。
The hairless SKH-1 mouse strain has a higher skin tumor incidence, shorter tumor latency, and higher tumor yield in response to ultraviolet (UV) irradiation than the SENCAR strain. In this study we assessed the differences in UV susceptibility of both strains by measuring DNA photodamage and epidermal proliferation after one UV treatment and after 1, 3, 6, and 9 wk of chronic UV irradiation, Induction rates for cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts [(6-4) PDs] were significantly greater in the SKH-1 strain than the SENCAR strain, but no strain differences in repair kinetics were detected for CPDs or (6-4) PDs, With chronic UV exposure we observed the following: (i) there was an equal amount of DNA photodamage in both strains; (ii) the number of (6-4) PDs was significantly greater than the CPDs after 6 wk; (iii) there were a significantly greater number of epidermal cells (1.5-fold increase) in the SKH-1 strain; (iv) the number of cycling cells, as measured by 5-bromo-2'-deoxyuridine (BrdU), were located both basally and suprabasally and were significantly greater in the SKH-1 strain; and (v) the number of cells immunoreactive to p53 was equivalent in both strains, but immunoreactive cells were located suprabasally in the SKH-1 strain after 9 wk of UV, These results show that the etiologic role of UV in tumorigenesis is dependent on events other than the amount of DNA photodamage in mouse epidermis.