Formation and removal of DNA adducts in target and nontarget tissues of rats administered multiple doses of 2-acetylaminophenanthrene.
Formation and removal of DNA adducts in target and nontarget tissues of rats administered multiple doses of 2-acetylaminophenanthrene.
复制标题
给予多剂量 2-乙酰氨基菲的大鼠靶组织和非靶组织中 DNA 加合物的形成和去除。
DOI：
10.1093/carcin/10.11.2025
复制
发表时间：
1989
期刊：
影响因子：
4.7
通讯作者：
Beland,FA
中科院分区：
文献类型：
--
作者：
Gupta,RC;Earley,K;Fullerton,NF;Beland,FA
2-乙酰氨基菲(2-AAP)对大鼠乳腺、小肠和耳道有致癌作用，但对肝癌无致癌作用。为了了解2-AAP诱导肿瘤的组织特异性，比较了2-AAP对靶组织和非靶组织中DNA加合物的形成和清除的影响。雄性和雌性SD大鼠均予腹腔注射。从所有组织中提取的DNA的32P-后标记分析显示有两个主要加合物(占总结合量的85%-95%)和至少四个次要加合物。通过比较N-羟基-2-氨基菲与脱氧核糖核酸在pH=5时的反应结果，确定了主要的加合物为asN(deoxyuguanosin-N-8-yl)-2-aminophenanthrene和L-(脱氧鸟苷-N-基)-2-氨基菲。在体外反应中还生成了两个次要加合物N-(脱氧腺苷-8-基)-2-氨基菲和L-(脱氧腺苷-6-基)-2-氨基菲。2-AAP在靶组织和非靶组织中的加合物分布、结合程度和加合物持久性相似，表明2-AAP的组织特异性除加合物形成外，还受多种因素的影响。
2-Acetylaminophenanthrene (2-AAP) is carcinogenic for the mammary gland, small intestine and ear duct in rats, but is not hepatocarcinogenic. In order to understand the tissue specificity of tumor induction, the formation and removal of DNA adducts in target and nontarget tissues have been compared in rats administered 2-AAP. Male and female Sprague-Dawley rats were treated i.p. with up to four weekly doses of 5 mg 2-AAP per kg body weight.32P-Post-labeling analysis of the DNA from all tissues showed two predominant adducts (>85–95% of the total binding) and at least four minor adducts. By comparing the results obtained from reactingN-hydroxy-2-aminophenanthrene with DNA at pH 5, the major adducts were identified asN(deoxyuguanosin-N-8-yl)-2-aminophenanthrene and l-(deoxyguanosin-N2-yl)-2-aminophenanthrene. Two minor adducts,N-(deoxy-adenosine-8-yl)-2-aininophenanthrene and l-(deoxyadenosin-iN6-yl)-2-aminophenanthrene, were also formed in thein vitroreactions. The distribution of adducts, extent of binding and adduct persistence were similar between target and nontarget tissues, which indicates that the tissue specificity of 2-AAP for tumor induction is due to factors hi addition to adduct formation.