Hayashi F, Tamura H, Watanabe T, Suga T
Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Science, Japan.
Cancer Lett. 1995 May 25;92(1):87-90. doi: 10.1016/0304-3835(95)03758-o.
Effects of [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14643) or di(2-ethylhexyl) phthalate (DEHP) as peroxisome proliferators on the susceptibility of liver DNA to damage by N-nitrosodimethylamine (DMN) or methyl methane sulfonate (MMS) were investigated. Male F344 rats were administered Wy-14643 or DEHP, orally, for 1 or 10 weeks. At 1 week, the susceptibility to hepatic DNA damage by DMN or MMS was significantly increased in the Wy-14643- or DEHP-treated rats. The enhancement of the susceptibility persisted for up to 10 weeks in both peroxisome proliferator-treated groups. These findings suggest that the high susceptibility to DNA damage caused by peroxisome proliferators would amplify the DNA damage action such as spontaneous damage, leading to an increase in the risk of initiation in the hepatocarcinogenesis.
研究了过氧化物酶体增殖剂[4-氯-6-(2,3-二甲基苯胺基)-2-嘧啶基硫代]乙酸（Wy-14643）或邻苯二甲酸二(2-乙基己基)酯（DEHP）对肝脏DNA受N-亚硝基二甲胺（DMN）或甲磺酸甲酯（MMS）损伤易感性的影响。雄性F344大鼠经口给予Wy-14643或DEHP，持续1周或10周。在1周时，Wy-14643或DEHP处理的大鼠对DMN或MMS引起的肝脏DNA损伤的易感性显著增加。在两个过氧化物酶体增殖剂处理组中，这种易感性的增强持续长达10周。这些发现表明，过氧化物酶体增殖剂引起的对DNA损伤的高易感性会放大诸如自发损伤等DNA损伤作用，导致肝癌发生起始风险增加。
