Metabolic activation of carcinogenic ethylbenzene leads to oxidative DNA damage
Metabolic activation of carcinogenic ethylbenzene leads to oxidative DNA damage
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DOI：
10.1016/j.cbi.2004.09.020
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发表时间：
2004-12-07
影响因子：
5.1
通讯作者：
Kojima, N
中科院分区：
文献类型：
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作者：
Midorikawa, K;Uchida, T;Kojima, N
乙苯对大鼠和小鼠有致癌性，但无致突变活性。我们已经研究了是否有代谢活化，导致DNA损伤。乙苯代谢为1-苯基乙醇、苯乙酮。2-乙基苯酚和4-乙基苯酚。此外，2-乙基苯酚和4-乙基苯酚被代谢转化为环二羟基化的代谢产物，如乙基氢醌和4-乙基儿茶酚，分别。用~（32）P标记的DNA片段实验表明，Cu（Ⅱ）存在时，乙基对苯二酚和4-乙基邻苯二酚均引起DNA损伤。这些二羟基化合物也诱导形成8-氧代-7，8-二氢-2 '-脱氧鸟苷在小牛胸腺DNA中的Cu（II）的存在下。过氧化氢酶、蛋氨酸和铜（I）特异性螯合剂浴铜灵显著（P
Ethylbenzene is carcinogenic to rats and mice, while it has no mutagenic activity. We have investigated whether ethylbenzene undergoes metabolic activation, leading to DNA damage. Ethylbenzene was metabolized to 1-phenylethanol, acetophenone. 2-ethylphenol and 4-ethylphenol by rat liver microsomes. Furthermore, 2-ethylphenol and 4-ethylphenol were metabolically transformed to ring-dihydroxylated metabolites such as ethylhydroquinone and 4-ethylcatechol, respectively. Experiment with 32 P-labeled DNA fragment revealed that both ethylhydroquinone and 4-ethylcatechol caused DNA damage in the presence of Cu(II). These dihydroxylated compounds also induced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in calf thymus DNA in the presence of Cu(II). Catalase, methional and Cu(I)-specific chelator, bathocuproine, significantly (P