Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/- mice.
Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/- mice.
复制标题
DOI：
--
复制
发表时间：
1999-02
期刊：
影响因子：
11.2
通讯作者：
D. Cheo;D. Burns;L. Meira;J. Houle;E. Friedberg
中科院分区：
文献类型：
--
作者：
D. Cheo;D. Burns;L. Meira;J. Houle;E. Friedberg
经过基因工程改造以模拟人类遗传性癌症易患DNA修复缺陷疾病色素性干皮病(XP)的小鼠非常容易患上紫外线辐射诱发的皮肤癌。然而，目前尚不清楚XP小鼠或人类是否易患与环境致癌物相关的其他组织中的癌症。为了测试核苷酸切除修复在防止内脏化学致癌中的重要性，我们用2-乙酰氨基荧和NOH-2-乙酰氨基荧来处理XPC突变(xpc-/-)小鼠。我们观察到，与正常和杂合子小鼠相比，化学诱导的XPC-/-小鼠肝和肺肿瘤的发生率显著增加。此外，与XPC-/-Trp53+/+小鼠相比，XPC-/-Trp53+/-小鼠的肝脏肿瘤进展更快。最后，我们证明了与XPC+/+Trp53-/-小鼠相比，XPC-/-TrpS3-/-双突变小鼠的自发性睾丸肿瘤发生率更高。
Mice that are genetically engineered to mimic the human hereditary cancer-prone DNA repair-defective disease xeroderma pigmentosum (XP) are highly predisposed to UV radiation-induced skin cancer. It is not clear, however, whether XP mice or humans are predisposed to cancers in other tissues associated with exposure to environmental carcinogens. To test the importance of nucleotide excision repair in protection against chemical carcinogenesis in internal organs, we treated XPC mutant (XPC-/-) mice with 2-acetylaminofluorene and NOH-2-acetylaminofluorene. We observed a significantly higher incidence of chemically induced liver and lung tumors in XPC-/- mice compared with normal and heterozygous littermates In addition, the progression of liver tumors in XPC-/- Trp53+/- mice is accelerated compared with XPC-/- Trp53+/+ animals. Finally, we demonstrate a higher incidence of spontaneous testicular tumors in XPC-/- TrpS3-/- double mutant mice compared with XPC+/+ Trp53-/- mice.