Gupta R C, Goel S K, Earley K, Singh B, Reddy J K
Carcinogenesis. 1985 Jun;6(6):933-6. doi: 10.1093/carcin/6.6.933.
Hepatocarcinogenic peroxisome proliferators, clofibrate, ciprofibrate, Wy-14643 or di(2-ethylhexyl)phthalate, were administered once daily by gavage to groups of three male F344 rats for 3 days and the rats were killed 2 h after the last dose. The DNA isolated from the livers was analyzed for possible carcinogen-DNA adducts, by a most sensitive 32P-postlabeling technique which can detect one adduct in 10(10) nucleotides. No adducts were detected by this assay in the DNA isolated from the livers of rats treated with any of the peroxisome proliferators. Adducts were also not found in the DNA of hepatocytes exposed in vitro to these peroxisome proliferators for 4 h in primary suspension cultures. Failure to detect peroxisome proliferator DNA adducts in hepatocytes under in vivo and in vitro conditions supports the contention that formation of a peroxisome proliferator-DNA adduct is not an essential step in the carcinogenesis by this novel class of carcinogens.
将致肝癌的过氧化物酶体增殖剂，即安妥明、环丙贝特、Wy-14643或邻苯二甲酸二（2-乙基己基）酯，每日一次经口灌胃给予每组3只雄性F344大鼠，持续3天，在最后一剂给药后2小时处死大鼠。采用一种极其灵敏的32P后标记技术分析从肝脏分离的DNA中是否存在可能的致癌物-DNA加合物，该技术能够检测出10（10）个核苷酸中的一个加合物。在用任何一种过氧化物酶体增殖剂处理的大鼠肝脏分离的DNA中，通过该检测未检测到加合物。在原代悬浮培养中，体外暴露于这些过氧化物酶体增殖剂4小时的肝细胞DNA中也未发现加合物。在体内和体外条件下均未能在肝细胞中检测到过氧化物酶体增殖剂DNA加合物，这支持了这样一种观点，即过氧化物酶体增殖剂-DNA加合物的形成并非这类新型致癌物致癌过程中的必要步骤。
