Maack C A, Silva M H, Petrakis N L, Lee R E, Lyon M
Carcinogenesis. 1986 Jun;7(6):899-905. doi: 10.1093/carcin/7.6.899.
Sprague-Dawley rat mammary gland is extremely sensitive to tumorigenesis by single or multiple doses of several polycyclic aromatic hydrocarbons. We obtained quantitative data on the in vitro mutagenic activation of several procarcinogens by 9000 g supernatant fraction (S9) from rat mammary gland using the Ames test. Mutagenic activation was shown to be dependent on a nicotinamide adenine dinucleotide phosphate (NADPH) generating system. An S9 preparation from mammary tissue of lactating Sprague-Dawley rats was shown to activate 2-aminoanthracene (2-AA). A polychlorinated biphenyl mixture of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) given to rats greatly raised the specific activity (revertant TA98 colonies/mg S9 protein) of the mammary tissue using 2-AA as a test carcinogen, and permitted detection of 2,4-diaminoanisole (DAA) and 2,7-diaminofluorene (DAF) activation. Procarcinogens 2-aminofluorine (2-AF), benzo[a]pyrene (BP) and aflatoxin (AFL) B1 were not detectably activated by mammary gland. Mutagenesis produced in mammary S9 activation of 2-AA, DAA or DAF was significantly inhibited by alpha-naphthoflavone (alpha NF) but was inhibited minimally by metyrapone (MP). Human mammary tumor cell lines (734B, SkBr3, MDA-MD-330) possessed inducible procarcinogen metabolizing activities similar to those found in S9 of rat mammary tissue. We demonstrated a simple and convenient use of the Ames test to characterize activation of many potential mutagens and carcinogens for mammary gland. When a test compound such as 2-AA was used, selective enzyme induction and inhibition was demonstrated.
斯普拉格-道利大鼠乳腺对单剂量或多剂量的几种多环芳烃诱导肿瘤生成极为敏感。我们使用艾姆斯试验，获得了大鼠乳腺9000g上清液组分（S9）对几种前致癌物进行体外诱变激活的定量数据。结果表明，诱变激活依赖于烟酰胺腺嘌呤二核苷酸磷酸（NADPH）生成系统。来自泌乳斯普拉格-道利大鼠乳腺组织的S9制剂可激活2-氨基蒽（2-AA）。给大鼠投喂2,3,7,8-四氯二苯并对二噁英（TCDD）的多氯联苯混合物，以2-AA作为测试致癌物时，大大提高了乳腺组织的比活性（回复突变TA98菌落数/毫克S9蛋白），并能检测到2,4-二氨基苯甲醚（DAA）和2,7-二氨基芴（DAF）的激活。前致癌物2-氨基芴（2-AF）、苯并[a]芘（BP）和黄曲霉毒素（AFL）B1未被乳腺显著激活。α-萘黄酮（α-NF）可显著抑制乳腺S9激活2-AA、DAA或DAF所产生的诱变作用，而美替拉酮（MP）的抑制作用最小。人乳腺肿瘤细胞系（734B、SkBr3、MDA-MD-330）具有与大鼠乳腺组织S9中相似的可诱导前致癌物代谢活性。我们证明了艾姆斯试验可简便地用于表征乳腺中许多潜在诱变剂和致癌物的激活情况。当使用测试化合物如2-AA时，可显示出选择性酶诱导和抑制作用。
