Le Curieux F, Munter T, Kronberg L
Department of Organic Chemistry, Abo Akademi University, Turku, Finland.
Chem Res Toxicol. 1997 Oct;10(10):1180-5. doi: 10.1021/tx970106g.
Calf thymus DNA was reacted with the extremely potent bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and the structurally related compounds 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA) and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF). The chromatograms of the HPLC analyses of the DNA hydrolysates showed peaks that represented adducted base moieties. It was possible to establish the structures of the adducts by comparing UV spectra and chromatographical properties of the DNA adducts with known adenosine and 2'-deoxyadenosine adducts. The DNA adduct produced by MX was identified as 3-(2'-deoxyribofuranosyl-N6-adenosinyl)propenal (M1A-dR). It was calculated that 1 nucleotide/10(5) nucleotides was converted to M1A-dR. The same adduct was formed also in the reaction of MX with 2'-deoxyadenosine (yield 0.01%). The M1A-dR adduct may play a role in the mutational events induced by MX in Salmonella typhimurium strain TP2428. The adducts produced in the reactions of MCA and MCF with DNA were identified as 3-(2'-deoxyribofuranosyl)-7-formylimidazo[2,1-i]purine (epsilon cA-dR) and 4-(2'-deoxyribofuranosyl-N6-adenosinyl)-3-formyl-3-butenoic acid (fbaA-dR), respectively. The yield of epsilon cA-dR was 5 adducts/ 10(6) nucleotides and of fbaA-dR 4 adducts/10(5) nucleotides. The biological significance of these adducts is unknown.
小牛胸腺DNA与极强的细菌诱变剂3-氯-4-(二氯甲基)-5-羟基-2(5H)-呋喃酮（MX）以及结构相关的化合物3,4-二氯-5-羟基-2(5H)-呋喃酮（MCA）和3-氯-4-甲基-5-羟基-2(5H)-呋喃酮（MCF）发生反应。DNA水解产物的高效液相色谱分析色谱图显示出代表加合碱基部分的峰。通过将DNA加合物的紫外光谱和色谱性质与已知的腺苷和2'-脱氧腺苷加合物进行比较，有可能确定加合物的结构。MX产生的DNA加合物被鉴定为3-(2'-脱氧核糖呋喃糖基-N6-腺苷基)丙烯醛（M1A-dR）。经计算，每10(5)个核苷酸中有1个核苷酸转化为M1A-dR。在MX与2'-脱氧腺苷的反应中也形成了相同的加合物（产率0.01%）。M1A-dR加合物可能在鼠伤寒沙门氏菌菌株TP2428中由MX诱导的突变事件中起作用。MCA和MCF与DNA反应产生的加合物分别被鉴定为3-(2'-脱氧核糖呋喃糖基)-7-甲酰基咪唑并[2,1-i]嘌呤（εcA-dR）和4-(2'-脱氧核糖呋喃糖基-N6-腺苷基)-3-甲酰基-3-丁烯酸（fbaA-dR）。εcA-dR的产率为每10(6)个核苷酸5个加合物，fbaA-dR的产率为每10(5)个核苷酸4个加合物。这些加合物的生物学意义尚不清楚。
