Viviani A, Lutz W K
Arch Toxicol Suppl. 1979(2):285-8. doi: 10.1007/978-3-642-67265-1_25.
The influence of microsomal (mAHH) and nuclear (nAHH) aryl hydrocarbon hydroxylase activity on the covalent binding of tritiated benzo(a)pyrene to rat liver DNA was evaluated in vivo. Induction of mAHH was obtained after phenobarbitone treatment (180% of control), which increased DNA binding to 210%, but left the nAHH unchanged. mAHH and nAHH were slightly induced with dieldrin (130% and 120%), but the binding remained unchanged. The increasing effect of mAHH as well as the possibly decreasing effect of nAHH induction on the binding became obvious when the data of 11 individual rats were used to solve the equation Binding = aX(mAHH) + bX(nAHH) + c. Multiple linear regression analysis resulted in positive values for a and c, a negative value for b, and a multiple correlation coefficient R = 0.82. An influence of other enzymes involved in the metabolism of benzo(a)pyrene cannot be excluded. The study shows clearly that the binding of a foreign compound to DNA in vivo is not only dependent on microsomal enzyme activities but also on nuclear activities even if the latter are considerably lower than those of microsomes.
在体内评估了微粒体(mAHH)和细胞核(nAHH)芳烃羟化酶活性对氚标记苯并(a)芘与大鼠肝脏DNA共价结合的影响。苯巴比妥处理后可诱导mAHH(为对照的180%),这使DNA结合增加至210%,但nAHH无变化。狄氏剂可轻微诱导mAHH和nAHH(分别为130%和120%),但结合情况保持不变。当用11只个体大鼠的数据求解方程“结合=a×(mAHH)+b×(nAHH)+c”时,mAHH对结合的增加作用以及nAHH诱导对结合可能的降低作用变得明显。多元线性回归分析得出a和c为正值,b为负值,复相关系数R = 0.82。不能排除参与苯并(a)芘代谢的其他酶的影响。该研究清楚地表明,体内外来化合物与DNA的结合不仅取决于微粒体酶活性,还取决于细胞核活性,即使后者远低于微粒体的活性。