de Vries A, van Oostrom C T, Dortant P M, Beems R B, van Kreijl C F, Capel P J, van Steeg H
Department of Immunology, University of Utrecht, The Netherlands.
Mol Carcinog. 1997 May;19(1):46-53.
Defects in the xeroderma pigmentosum complementation group A-correcting (XPA) gene, which encodes a component of the nucleotide excision repair (NER) pathway, are associated with the cancer-prone human disease xeroderma pigmentosum. We previously generated mice lacking the XPA gene, which develop normally but are highly sensitive to ultraviolet-B and 7,12-dimethylbenz[a] anthracene-induced skin tumors. Here we report that XPA-deficient mice spontaneously developed hepatocellular adenomas at a low frequency as they aged. Furthermore, oral treatment of XPA-deficient mice with the carcinogen benzo[a]pyrene (B[a]P) resulted in the induction of mainly lymphomas. These tumors appeared earlier and with a higher incidence than in B[a]P-treated wild-type and heterozygous mice. Our results show for the first time that XPA-deficient mice also displayed an increased sensitivity to developing tumors other than tumors of the skin.
着色性干皮病互补组A校正（XPA）基因存在缺陷，该基因编码核苷酸切除修复（NER）途径的一个组分，与易患癌症的人类疾病着色性干皮病相关。我们之前培育出了缺乏XPA基因的小鼠，这些小鼠发育正常，但对紫外线B和7,12-二甲基苯并[a]蒽诱导的皮肤肿瘤高度敏感。在此我们报告，XPA基因缺陷的小鼠随着年龄增长会以低频率自发发生肝细胞腺瘤。此外，用致癌物苯并[a]芘（B[a]P）对XPA基因缺陷的小鼠进行口服治疗，主要诱导产生淋巴瘤。这些肿瘤比用B[a]P处理的野生型和杂合小鼠出现得更早，且发病率更高。我们的结果首次表明，XPA基因缺陷的小鼠对发生除皮肤肿瘤之外的其他肿瘤也表现出更高的敏感性。
