Blons H, Radicella J P, Laccourreye O, Brasnu D, Beaune P, Boiteux S, Laurent-Puig P
Laboratoire de Toxicologie Moléculaire, Université René Descartes, Paris, France.
Mol Carcinog. 1999 Dec;26(4):254-60.
Cigarette smoking is the major known risk factor for head and neck cancer. Tobacco promotes oxidative stress and enhances tissue levels of 8-hydroxyguanine (8-OH-G) in smokers. The presence of 8-OH-G does not impede replication but leads to an accumulation of G-->T transversions. Recently, the gene for human 8-oxoguanine DNA glycosylase 1 (hOGG1), an enzyme involved in the repair of 8-OH-G in humans, was cloned and mapped to chromosome 3p. In head and neck tumors, the hOGG1 gene locus is often targeted by loss of heterozygosity (LOH), and the spectrum of mutations in the p53 gene shows a bias in favor of G:C-->T:A transversions, as would be expected if HOGG1 repair functions were disabled. To test the involvement of hOGG1 in head and neck carcinogenesis, we had previously screened 56 tumors for LOH at 3p. From these tumors and two others, we selected 33 tumors demonstrating LOH for further mutational analysis of this gene. No somatic inactivating mutation was found in hOGG1. Polymorphisms involving intron 4 and exon 7 were present in 30% of the patients. A new polymorphism was identified in one patient in exon 6 and led to the amino-acid change G308E. Similar repair activities were found for the wild-type and exon 6-variant enzymes. Therefore, the involvement of hOGG1 in head and neck carcinogenesis is not strongly supported by this work.
吸烟是已知的头颈部癌症的主要风险因素。烟草会促进氧化应激并提高吸烟者体内8-羟基鸟嘌呤（8-OH-G）的组织水平。8-OH-G的存在并不妨碍复制，但会导致G→T颠换的积累。最近，人类8-氧代鸟嘌呤DNA糖基化酶1（hOGG1）的基因被克隆并定位到3号染色体短臂，该酶参与人类8-OH-G的修复。在头颈部肿瘤中，hOGG1基因位点常因杂合性缺失（LOH）而成为靶点，并且p53基因的突变谱显示出偏向于G:C→T:A颠换的倾向，正如如果HOGG1修复功能被禁用所预期的那样。为了测试hOGG1在头颈部癌变中的作用，我们之前对56个肿瘤进行了3号染色体短臂杂合性缺失的筛查。从这些肿瘤和另外两个肿瘤中，我们选择了33个显示杂合性缺失的肿瘤，对该基因进行进一步的突变分析。在hOGG1中未发现体细胞失活突变。30%的患者存在涉及内含子4和外显子7的多态性。在一名患者的外显子6中发现了一种新的多态性，导致氨基酸改变G308E。野生型和外显子6变异型酶具有相似的修复活性。因此，这项研究并未有力支持hOGG1参与头颈部癌变的观点。
