Scribner J D, Mottet N K
Carcinogenesis. 1981;2(12):1235-9. doi: 10.1093/carcin/2.12.1235.
2-Acetamidophenanthrene (AAP) yields adducts to rat liver DNA and RNA in amounts comparable to those found for the potent hepatocarcinogen 2-acetamidofluorene, but is not hepatocarcinogenic. This suggested that AAP might initiate liver tumors, but was incapable of causing their progression to a detectable state. To test this hypothesis, the protocol devised by Peraino was used, in which 21-day-old male Sprague-Dawley rats were fed 0.02% AAP in a grain diet for three weeks. this was followed by long-term feeding of 0.05% 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT). The mean latent period of all tumors (primarily mammary tumors) was reduced about six months by the DDT feeding. No tumors were found in rats treated with DDT only. Livers in all animals appeared normal at autopsy or on laparotomy, and showed barely detectable signs of toxicity upon histological examination. Thus, we have found that a once wide-spread environmental chemical acts as a tumor accelerator on a major target for human tumors. Because this finding is in the male rat, the significance of this result for breast cancer in women is uncertain.
2-乙酰氨基菲(AAP)与大鼠肝脏DNA和RNA形成加合物的量与强效肝癌致癌物2-乙酰氨基芴相当,但它并无致癌性。这表明AAP可能引发肝脏肿瘤,但无法使其发展到可检测状态。为验证这一假设,采用了佩拉伊诺设计的实验方案,即给21日龄雄性斯普拉格-道利大鼠喂食含0.02% AAP的谷物饲料,持续三周。之后长期喂食0.05%的1,1,1-三氯-2,2-双(4-氯苯基)乙烷(滴滴涕)。滴滴涕喂养使所有肿瘤(主要是乳腺肿瘤)的平均潜伏期缩短了约6个月。仅接受滴滴涕处理的大鼠未发现肿瘤。所有动物在尸检或剖腹检查时肝脏外观正常,组织学检查显示仅有难以察觉的毒性迹象。因此,我们发现一种曾经广泛存在的环境化学物质对人类肿瘤的一个主要靶器官起肿瘤促进剂的作用。由于这一发现是在雄性大鼠中得出的,该结果对女性乳腺癌的意义尚不确定。