Rice J E, Defloria M C, Sensenhauser C, Lavoie E J
Rutgers University, College of Pharmacy, Department of Pharmaceutical Chemistry, Piscataway, NJ 08854.
Chem Biol Interact. 1988;68(1-2):127-36. doi: 10.1016/0009-2797(88)90011-7.
The effect of the cocarcinogen fluoranthene on the DNA binding and metabolism of [3H]benzo[a]pyrene (B[a]P) in vivo in mouse skin has been investigated. In the presence of fluoranthene the level of B[a]]P-DNA binding was increased at each of the time intervals examined (4, 8, 24 and 48 h) with enhancements ranging from 76% at 4 h to 36% at 48 h. The ratio of anti-7,8,-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE)-DNA adducts/syn-BPDE-DNA adducts was also increased in the presence of fluoranthene. This increase was greatest at 8 h (44%) but by 48 h the ratio was identical in the presence and absence of fluoranthene. The observed increase in anti-BPDE-DNA adducts/syn-BPDE-DNA adducts did not parallel increases in B[a]P-DNA binding suggesting that alteration of the anti-BPDE/syn-BPDE ratio is not a major contributing factor to the cocarcinogenic activity of fluoranthene. The influence of fluoranthene on the metabolism of B[a]P in vivo in mouse skin was also investigated. Fluoranthene was found to have little or no effect on the formation of ethyl acetate extractable metabolites of B[a]P in mouse skin. Specifically, there was no increase in the amount of B[a]P-7,8-diol in the presence of fluoranthene. Fluoranthene also had little or no effect on the levels of beta-glucuronide or sulfate conjugates of B[a]P metabolites formed in vivo in mouse skin. These studies suggest that the effect of fluoranthene is being expressed at some point after B[a]P has been activated to an ultimate carcinogen.
已对辅助致癌物荧蒽对小鼠皮肤中[3H]苯并[a]芘（B[a]P）的DNA结合及体内代谢的影响进行了研究。在荧蒽存在的情况下，在所检测的各个时间间隔（4、8、24和48小时），B[a]P-DNA结合水平均有所升高，增幅范围从4小时时的76%到48小时时的36%。在荧蒽存在时，反式-7,8-二羟基-9,10-环氧-7,8,9,10-四氢苯并[a]芘（反式-BPDE）-DNA加合物与顺式-BPDE-DNA加合物的比例也有所增加。这种增加在8小时时最大（44%），但到48小时时，在有和没有荧蒽的情况下该比例相同。观察到的反式-BPDE-DNA加合物与顺式-BPDE-DNA加合物比例的增加与B[a]P-DNA结合的增加并不平行，这表明反式-BPDE/顺式-BPDE比例的改变并非荧蒽促癌活性的主要促成因素。还研究了荧蒽对小鼠皮肤中B[a]P体内代谢的影响。发现荧蒽对小鼠皮肤中B[a]P的乙酸乙酯可提取代谢物的形成几乎没有影响。具体而言，在荧蒽存在时，B[a]P-7,8-二醇的量没有增加。荧蒽对小鼠皮肤中体内形成的B[a]P代谢物的β-葡萄糖醛酸苷或硫酸盐结合物水平也几乎没有影响。这些研究表明，荧蒽的作用在B[a]P被激活成为最终致癌物之后的某个时间点才得以体现。
