Hutton J J, Meier J, Hackney C
Mutat Res. 1979 Jan;66(1):75-94. doi: 10.1016/0165-1218(79)90010-7.
Homogenates of liver, lung, kidney, stomach, small intestine and colon from 8 strains of mice were compared for their ability to metabolize benzo[a]pyrene (BP) and dimethylnitrosamine (DMN) to mutagens. Females of strains CF1, AKR/J, AU/SsJ, DBA/2J, SWR/J, A/J, C3H/HeJ, and C57BL/6J were either untreated or received phenobarbital (PB), 3-methylcholanthrene (MC) or polychlorinated biphenyls (AR) to induce drug-metabolizing enzymes. The effects of these drugs on organ weight and on the amounts of DNA, S-10 protein, and microsomal protein per unit weight of tissue are reported. Salmonella typhimurium TA92 and TA98 were used as indicators of the formation of mutagens. For each organ there was an optimal balance between amount of tissue homogenate and concentration of test compound for maximal yield of revertants. A sensitive radiometric assay of DMN demethylase (DMND) is described which permits measurement of the enzyme in liver, lung and kidney. DMN at 1 mM is used as substrate. Aryl hydrocarbon hydroxylase (AHH) was measured in all tissue using BP as substrate. AR and MC are very good inducers of AHH activity in livers of mice classified as aromatic hydrocarbon responsive, but not in those classified as hydrocarbon nonresponsive. Responsiveness is strain-specific and genetically regulated. Metabolism of BP to mutagens by liver homogenates was correlated with extent of AHH induction. This dimorphism of response of AHH to inducers was present, but less pronounced, in non-hepatic tissues. Basal activities of AHH and DMND were correlated in livers and lungs from untreated mice. DMND activities were increased less than 2-fold by PB, MC or AR treatments. Metabolism of DMN to mutagens was not closely correlated with DMND activities. Strain of mouse, type of tissue and test substance are important variables in assessing the potential effect of microsomal enzyme-inducing agents on the metabolism of mutagenic substances.
比较了8个品系小鼠的肝、肺、肾、胃、小肠和结肠匀浆代谢苯并[a]芘（BP）和二甲基亚硝胺（DMN）生成诱变剂的能力。CF1、AKR/J、AU/SsJ、DBA/2J、SWR/J、A/J、C3H/HeJ和C57BL/6J品系的雌性小鼠要么不接受处理，要么接受苯巴比妥（PB）、3-甲基胆蒽（MC）或多氯联苯（AR）以诱导药物代谢酶。报告了这些药物对器官重量以及单位重量组织中DNA、S-10蛋白和微粒体蛋白含量的影响。鼠伤寒沙门氏菌TA92和TA98用作诱变剂形成的指示菌。对于每个器官，组织匀浆量和测试化合物浓度之间存在最佳平衡，以实现回复突变体的最大产量。描述了一种灵敏的DMN脱甲基酶（DMND）放射性测定法，该方法可用于测量肝、肺和肾中的该酶。以1 mM的DMN作为底物。使用BP作为底物在所有组织中测量芳烃羟化酶（AHH）。AR和MC是被归类为芳烃反应性小鼠肝脏中AHH活性的非常好的诱导剂，但在被归类为非烃反应性的小鼠肝脏中则不是。反应性具有品系特异性且受遗传调控。肝匀浆将BP代谢为诱变剂与AHH诱导程度相关。AHH对诱导剂反应的这种二态性在非肝组织中也存在，但不太明显。未处理小鼠肝脏和肺中AHH和DMND的基础活性相关。PB、MC或AR处理使DMND活性增加不到2倍。DMN代谢为诱变剂与DMND活性没有密切相关。小鼠品系、组织类型和测试物质是评估微粒体酶诱导剂对诱变物质代谢潜在影响的重要变量。
