Lutz W K, Viviant A, Schlatter C
Cancer Res. 1978 Mar;38(3):575-8.
With radioactive compounds of high specific activity, the binding of carcinogens to DNA can be measured with doses that are ineffective in long-term studies. The binding of tritiated benzo(a)pyrene to liver DNA of adult male rats has been determined 50 hr after a single i.p. injection of doses between 40 microgram/kg and 4 mg/kg. The dose-response relationship is linear up to 1 mg/kg, shows a step towards 2 mg/kg, and gives a shallow linear slope above that value. The observed binding ranges from 1.7 to 180 nmoles benzo(a)pyrene per mole DNA phosphate. The nonlinearity could be due to an induction of metabolizing enzymes. The microsomal aryl hydrocarbon hydroxylase activity increases significantly 24 hr after a single dose of 4 mg/kg and 48 hr after doses of 2 and 4 mg/kg, but no induction is found with 1 mg/kg. The binding from an equimolar dose is 35 times lower than the one found on mouse skin DNA and 300 times lower than that of N,N-dimethylnitrosamine in rat liver. A good correlation exists to the respective tumor formation in long-term studies.
使用高比活度的放射性化合物，在长期研究中无效的剂量下就可以测量致癌物与DNA的结合。在成年雄性大鼠单次腹腔注射40微克/千克至4毫克/千克剂量的50小时后，已测定了氚化苯并(a)芘与肝脏DNA的结合情况。在1毫克/千克以下，剂量-反应关系呈线性，在2毫克/千克时出现一个台阶，高于该值时呈浅线性斜率。观察到的结合量范围为每摩尔DNA磷酸1.7至180纳摩尔苯并(a)芘。这种非线性可能是由于代谢酶的诱导。单次剂量4毫克/千克后24小时以及剂量2毫克/千克和4毫克/千克后48小时，微粒体芳烃羟化酶活性显著增加，但1毫克/千克剂量未发现诱导现象。等摩尔剂量的结合量比在小鼠皮肤DNA上发现的低35倍，比大鼠肝脏中N,N-二甲基亚硝胺的低300倍。在长期研究中，与各自的肿瘤形成存在良好的相关性。
