DNA adduct formation of the food carcinogen 2-amino-3-methylimidazo[4,5- f]quinoline at the C-8 and N2 atoms of guanine.
DNA adduct formation of the food carcinogen 2-amino-3-methylimidazo[4,5- f]quinoline at the C-8 and N2 atoms of guanine.
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食品致癌物 2-氨基-3-甲基咪唑并[4,5-f]喹啉在鸟嘌呤的 C-8 和 N2 原子处形成 DNA 加合物。
DOI：
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发表时间：
1994
影响因子：
4.1
通讯作者：
J. Markovic
中科院分区：
文献类型：
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作者：
R. Turesky;J. Markovic
用~(32)P后标记法研究了2-氨基-3-甲基咪唑并[4，5-f]喹啉(IQ)的DNA加合物形成。体外用可能致癌的代谢物N2-acetoxyamino-3-methylimidazo[4，5-f]-quinoline(N-乙酰氧基-IQ)修饰的小牛胸腺DNA和IQ处理的大鼠肝DNA的加合物图谱相似。在标记后的条件下，N-(Deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4，5-f]quinoline(DG-C8-IQ)约占标记后条件下观察到的小牛胸腺DNA总加合物的90%；然而，只有当5-(deoxyguanosin-N2-yl)-2-amino-3-methylimidazo[4，5-被过量标记时，才能检测到DG f]喹啉(DG-n2-IQ)。在此标记条件下，DG-C8-IQ和DG-N2-IQ分别约占总加合物的75%和7%。其他五个地点造成了剩余的放射性。从大鼠肝DNA中也得到了类似的结果。用固相萃取富集DNA加合物后，DG-C8-IQ和DG-N2-IQ分别占大鼠肝脏总加合物的60-76%和10-13%。2‘-脱氧鸟苷3’-单磷酸(DG-3‘-PO4-)与IQ的光活化叠氮衍生物2-叠氮基-3-甲基咪唑并[4，5-f]喹啉(N3-IQ)反应得到的加合产物与N-乙酰氧基-IQ反应得到的加合物轮廓定性相似。C-8和N_2加合物是唯一检测到的反应产物。加合物取代的反应活性和位置依赖于溶剂条件和pH，在碱性pH下加合物的形成增加。光活化的N3-IQ与DG-3‘-PO4-在水、柠檬酸盐缓冲液(pH 5.0)或磷酸盐缓冲液(pH 7.4)中的化学反应活性明显高于N-乙酰氧基IQ。反应活性的提高归因于DG-C8-IQ加合物形成水平的增加，但在柠檬酸缓冲液(pH 5.0)中进行的反应除外，在那里C-8和N2鸟嘌呤加合物都成比例增加。但在磷酸盐缓冲液(pH 9.0)中，这两种IQ衍生物的化学反应活性和它们的DG取代部位是相同的。在含有N3-IQ的反应中，DG-N2-IQ加合物占总加合物的比例在碱性pH下增加，但对于N-乙酰氧基-IQ反应，这一比例不受介质pH变化的影响。对于同时涉及N-乙酰氧基-IQ和N3-IQ的反应，DG-N-IQ加合物占总加合物的比例也随着磷酸盐浓度的增加而增加。(摘要截短400字)
DNA adduct formation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has been investigated by 32P-postlabeling. Similar adduct profiles were observed from calf thymus DNA modified in vitro with the putative carcinogenic metabolite N2-acetoxyamino-3-methylimidazo[4,5-f]-quinoline (N-acetoxy-IQ) and from hepatic DNA of rats treated with IQ. N-(Deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ) accounted for approximately 90% of the total adducts observed in calf thymus DNA under postlabeling conditions where ATP was limiting; however, 5-(deoxyguanosin-N2-yl)-2-amino-3-methylimidazo[4,5- f]quinoline (dG-N2-IQ) was detected only when DNA was labeled with excess ATP. Under these labeling conditions, dG-C8-IQ and dG-N2-IQ accounted for approximately 75% and 7% of the total adducts, respectively. Five other spots accounted for the remaining radioactivity. Comparable results were obtained from rat liver DNA. Following DNA adduct enrichment by solid phase extraction, dG-C8-IQ and dG-N2-IQ accounted for 60-76% and 10-13%, respectively, of the total adducts in rat liver. The adduct profiles obtained from reaction of 2'-deoxyguanosine 3'-monophosphate (dG-3'-PO4-) with the photoactivated azide derivative of IQ, 2-azido-3-methylimidazo[4,5-f]quinoline (N3-IQ), were qualitatively similar to those obtained by reaction with N-acetoxy-IQ. The C-8 and N2 adducts were the only reaction products detected. The reactivity and sites of adduct substitution were dependent upon solvent conditions and pH, with increasing adduct formation under alkaline pH. The chemical reactivity of photoactivated N3-IQ with dG-3'-PO4- was significantly greater than that of N-acetoxy-IQ when reactions were conducted in water, in citrate buffer (pH 5.0), or in phosphate buffer (pH 7.4). Increased reactivity was attributed to increased levels of dG-C8-IQ adduct formation, except for reactions conducted in citrate buffer (pH 5.0), where there was a proportional increase in both C-8 and N2 guanine adducts. However, the chemical reactivity of these two IQ derivatives and their sites of dG substitution were identical when the reactions were conducted in phosphate buffer (pH 9.0). The ratio of the dG-N2-IQ adduct to the total adducts increased at alkaline pH in reactions involving N3-IQ, but the ratio was not affected by a change in the pH of the medium for reactions with N-acetoxy-IQ. The ratio of the dG-N2-IQ adduct to the total adducts also increased as a function of phosphate concentration for reactions involving both N-acetoxy-IQ and N3-IQ.(ABSTRACT TRUNCATED AT 400 WORDS)