K-ras cancer gene mutations in lung tumors from female Swiss (CD-1) mice exposed transplacentally to 3'-azido-3'-deoxythymidine.
K-ras cancer gene mutations in lung tumors from female Swiss (CD-1) mice exposed transplacentally to 3'-azido-3'-deoxythymidine.
复制标题
经胎盘暴露于 3-叠氮基-3-脱氧胸苷的雌性瑞士 (CD-1) 小鼠肺部肿瘤中的 K-ras 癌症基因突变。
DOI：
10.1002/em.20420
复制
发表时间：
2008
影响因子：
2.8
通讯作者：
Sills,RobertC
中科院分区：
文献类型：
--
作者：
Koujitani,Takatoshi;Ton,Tai-VuT;Lahousse,StephanieA;Hong,Hue-HuaL;Wakamatsu,Nobuko;Sills,RobertC
通过将怀孕的瑞士 (CD-1) 小鼠在妊娠期间（18-19 天）每天暴露于 0、50、100、200 或 300 毫克 3'-叠氮基-3'-脱氧胸苷 (AZT)/kg 体重 (BW) 进行经胎盘致癌性研究 [国家毒理学计划，2006]。 200 mg/kg 和 300 mg/kg 组中，雄性后代的肺泡/细支气管腺瘤和癌的发生率显着较高（分别为 P= 0.027 和 0.007），但在雌性后代中则不然（P= 0.338 和 0.315）。本研究的目的是评估 AZT 暴露组雌性后代肺肿瘤中 K-ras 突变的状态，并确定在分子水平上肺肿瘤中是否存在与自发性肿瘤不同的特征性 K-ras 突变。通过对从福尔马林固定、石蜡包埋的肺肿瘤中分离出的聚合酶链式反应 (PCR) 扩增 DNA 进行循环测序来检测 K-突变。在 AZT 暴露组的雌性后代的 28 个肺肿瘤中，有 17 个 (61%) 检测到 K-突变。在女性对照组检查的 8 个肿瘤中未检测到 K-突变。 50、100和300 mg/kg组中主要突变是密码子12 G→T颠换，200和300 mg/kg组中主要突变是密码子12 G→C颠换。 K-rasCodon 12 G→T 颠换（TGT 突变）可能是由氧化 DNA 损伤和 8-oxoG 诱导的，而 K-rasCodon 12 G→C 颠换（CGT 突变）可能是由于鸟嘌呤和 8-oxoG 的进一步氧化损伤。环境。摩尔。 Mutagen.，2008。2008 年出版 Wiley‐Liss, Inc.
A transplacental carcinogenicity study was conducted by exposing pregnant Swiss (CD‐1) mice to 0, 50, 100, 200, or 300 mg 3′‐azido‐3′‐deoxythymidine (AZT)/kg body weight (BW) daily for the duration of gestation (18–19 days) [National Toxicology Program,2006]. The incidence of alveolar/bronchiolar adenomas and carcinomas in the 200 and 300 mg/kg groups was significantly higher (P= 0.027 and 0.007, respectively) in male offspring, but not in females (P= 0.338 and 0.315, respectively). The purpose of the present study was to evaluate K‐rasmutation status in lung tumors from the female offspring in AZT exposed groups and to determine whether at the molecular level there were signature K‐rasmutations in lung tumors that were different from spontaneous tumors. K‐rasmutation was detected by cycle sequencing of polymerase chain reaction (PCR)‐amplified DNA, isolated from formalin‐fixed, paraffin‐embedded lung tumors. K‐rasmutations were detected in 17 of 28 (61%) lung tumors from the female offspring in AZT exposed groups. No K‐rasmutations were detected in the 8 tumors examined from the female control group. The predominant mutations were Codon 12 G→T transversions in the 50, 100, and 300 mg/kg groups, and Codon 12 G→C transversions in the 200 and 300 mg/kg groups. K‐rasCodon 12 G→T transversions (TGT mutations) may be induced by oxidative DNA damage and 8‐oxoguanine (8‐oxoG), while K‐rasCodon 12 G→C transversions (CGT mutations) may be due to further oxidative lesions of guanine and 8‐oxoG. Environ. Mol. Mutagen., 2008. Published 2008 Wiley‐Liss, Inc.