DNA adduct formation in mouse tissues in relation to serum levels of benzo(a)pyrene-diol-epoxide after injection of benzo(a)pyrene or the diol-epoxide.
DNA adduct formation in mouse tissues in relation to serum levels of benzo(a)pyrene-diol-epoxide after injection of benzo(a)pyrene or the diol-epoxide.
复制标题
注射苯并(a)芘或二醇-环氧化物后，小鼠组织中DNA加合物的形成与苯并(a)芘-二醇-环氧化物的血清水平相关。
作者：
G. Ginsberg;T. Atherholt
已有研究表明，小鼠注射B（a）P后，苯并（a）芘[B（a）P]的致癌代谢产物B（a）P-7，8-二醇-9，10-环氧化合物（BPDE）可在血清中转运。血清转运可能是致癌代谢物的重要来源，并导致组织中DNA加合物的形成。通过比较雌性C57 BL/6 x C3 H F1小鼠腹腔注射（2、20或200 mg/kg）B（a）P后血清中BPDE出现的时间过程与BPDE/DNA加合物形成的时间过程，研究了这种可能性。此外，静脉注射BPDE（8.25 nmol），并随后从血清中消失和组织DNA的加合。BPDE血清水平和DNA加合物水平通过32 P-后标记分析测量。结果表明，在腹腔注射200 mg B（a）P/kg后，肝脏、肺、肾脏、胃和脾脏中的BPDE/DNA加合物水平在5 h内急剧升高，然后在24 h内逐渐升高。24 h时，所有组织中的加合物水平相似。血清中的BPDE水平在2.5小时内达到平台期，此后保持恒定（10至11 nM）。血清中的B（a）P水平从1 h时的1980 nM稳定下降至24 h时的350 nM。在B（a）P i. p.剂量低10倍和100倍时，血清BPDE和DNA加合物水平显示出相似的剂量依赖性。静脉注射BPDE后，血清中的BPDE水平在5分钟内下降至初始水平的0.16%。此时，BPDE/DNA加合物在所有组织中均处于峰值水平。肺加合物水平比其他组织高10至100倍。这些结果支持BPDE的血清转运在B（a）P后DNA加合物产生中的作用，因为BPDE在DNA加合物形成的整个时间过程中均可在血清中获得。此外，注射的BPDE迅速形成DNA加合物，这主要发生在肺中，肺最容易接触转运的致癌物。
Previous studies have shown that the carcinogenic metabolite of benzo(a)pyrene [B(a)P], B(a)P-7,8-diol-9,10-epoxide (BPDE), is transported in serum after B(a)P injection in mice. It is possible that serum transport is an important source of carcinogenic metabolite and results in DNA adduct formation in tissues. This possibility was studied by comparing the time course for BPDE appearance in serum with that for BPDE/DNA adduct formation after B(a)P i.p. injection (2, 20, or 200 mg/kg) into female C57BL/6 x C3H F1 mice. Additionally, BPDE was injected i.v. (8.25 nmol), and its disappearance from serum and adduction of tissue DNA were followed. BPDE serum levels and DNA adduct levels were measured by 32P-postlabeling analysis. Results indicate that, after a 200-mg B(a)P/kg i.p. injection, BPDE/DNA adduct levels rose sharply in liver, lung, kidney, stomach, and spleen through 5 h and then more gradually through 24 h. Adduct levels were similar in all tissues at 24 h. BPDE levels in serum reached a plateau within 2.5 h and remained constant thereafter (10 to 11 nM). B(a)P levels in serum fell steadily from 1980 nM at 1 h to 350 nM by 24 h. Levels of serum BPDE and DNA adducts showed a similar dose dependency at 10- and 100-fold lower B(a)P i.p. doses. After BPDE i.v. injection, BPDE levels in serum decreased to 0.16% of the initial level within 5 min. By this time, BPDE/DNA adducts were at peak levels in all tissues assayed. Lung adduct levels were 10 to 100 times greater than those in the other tissues. These results support a role for serum transport of BPDE in the production of DNA adducts after B(a)P since BPDE was available in serum throughout the time course for DNA adduct formation. Further, injected BPDE rapidly formed DNA adducts and this occurred primarily in the lung, which had the greatest access to the transported carcinogen.