Reiners J J, Crowe D, McKeown C, Nerland D E, Sonnenfeld G
Carcinogenesis. 1984 Jan;5(1):125-8. doi: 10.1093/carcin/5.1.125.
In vivo induction of gamma interferon (IFN-gamma) by sensitization of mice with Mycobacterium bovis strain BCG and subsequent challenge with tuberculin depressed the ability of liver homogenates from treated animals to metabolically activate promutagens. The Ames Salmonella typhimurium revertant assay was used for analyses of metabolic conversion of promutagens by liver homogenates. Relative to the mutant frequencies determined with control liver homogenates, induction of IFN-gamma depressed the abilities of homogenates from treated animals to activate N-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), and benzo[a]pyrene (BP) by 55%, 44% and 95%, respectively. Within 18-24 h of Aroclor 1254 treatment, liver P-450 content had increased 43%, and the relative mutant yields per unit protein for all three promutagens had approximately doubled. In vivo induction of IFN-gamma suppressed the Aroclor 1254-dependent increases in mutagenesis by AAF (63%), AFB1 (90%), and BP (reduced to a level 23% below non-Aroclor 1254 treatment). In all cases, the levels of depression of promutagen activation qualitatively correlated with cytochrome P-450 content and the induction of IFN-gamma.
用牛分枝杆菌卡介苗菌株致敏小鼠并随后用结核菌素攻击，在体内诱导γ干扰素（IFN-γ），降低了处理动物肝脏匀浆代谢活化前诱变剂的能力。采用鼠伤寒沙门氏菌艾姆斯回复突变试验分析肝脏匀浆对前诱变剂的代谢转化。相对于用对照肝脏匀浆测定的突变频率，IFN-γ的诱导分别使处理动物匀浆激活N-乙酰氨基芴（AAF）、黄曲霉毒素B1（AFB1）和苯并[a]芘（BP）的能力降低了55%、44%和95%。在多氯联苯1254处理18 - 24小时内，肝脏P-450含量增加了43%，所有三种前诱变剂每单位蛋白质的相对突变产量大约增加了一倍。体内IFN-γ的诱导抑制了多氯联苯1254依赖性的AAF（63%）、AFB1（90%）诱变增加以及BP诱变（降低到比未用多氯联苯1254处理低23%的水平）。在所有情况下，前诱变剂活化的抑制水平与细胞色素P-450含量和IFN-γ的诱导在质量上相关。
