Melikian A A, Leszczynska J M, Hecht S S, Hoffmann D
Carcinogenesis. 1986 Jan;7(1):9-15. doi: 10.1093/carcin/7.1.9.
We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene) on the metabolic activation of [3H] benzo[a]pyrene (BaP) in mouse skin, in vivo and on the binding of BaP metabolites to DNA and protein at intervals from 0.5-24 h. Upon topical application of 0.015 mg [3H]BaP and 0.25 or 0.5 mg catechol per mouse, catechol had little effect on the total amount of [3H]BaP metabolized in mouse skin, but it affected the relative proportions of [3H]BaP metabolites. Catechol (0.5 mg/mouse) decreased the proportion of water-soluble [3H]BaP metabolites, ethyl acetate-soluble polar metabolites and quinones, but doubled the levels of unconjugated 3-hydroxy-BaP at all measured intervals after treatment. Catechol also caused a small increase in the levels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP 0.5 h after treatment. Two hours after treatment, the levels of these metabolites subsided to those of the controls. Catechol did not affect the levels of glutathione conjugates of BaP. However, it caused a decrease in glucuronide and sulphate conjugate formation from BaP. Catechol caused an approximately 2-fold increase in the formation of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroBaP (BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNA adducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivity associated with epidermal proteins after [3H]BaP application. Because catechol increased levels of 3-hydroxyBaP, we considered the possibility that 3-hydroxyBaP might enhance the tumor initiating activities of BaP or BPDE in mouse skin; a bioassay demonstrated that this was not the case. The results of this study indicate that one important effect of catechol related to its co-carcinogenicity is its ability to enhance formation of anti-BPDE-DNA adducts in mouse skin.
我们研究了助致癌物邻苯二酚（1,2 - 二羟基苯）对小鼠皮肤中[3H]苯并[a]芘（BaP）体内代谢活化的影响，以及在0.5 - 24小时的不同时间间隔下BaP代谢产物与DNA和蛋白质的结合情况。每只小鼠局部涂抹0.015 mg [3H]BaP和0.25或0.5 mg邻苯二酚后，邻苯二酚对小鼠皮肤中[3H]BaP代谢的总量影响不大，但影响了[3H]BaP代谢产物的相对比例。邻苯二酚（0.5 mg/小鼠）降低了水溶性[3H]BaP代谢产物、乙酸乙酯可溶性极性代谢产物和醌类的比例，但在处理后的所有测量时间间隔内，未结合的3 - 羟基 - BaP水平增加了一倍。邻苯二酚还使处理后0.5小时反式 - 7,8 - 二羟基 - 7,8 - 二氢BaP和反式 - 9,10 - 二羟基 - 9,10 - 二氢BaP的水平略有增加。处理后两小时，这些代谢产物的水平降至对照水平。邻苯二酚不影响BaP的谷胱甘肽结合物水平。然而，它导致BaP的葡糖醛酸和硫酸盐结合物形成减少。邻苯二酚使反式 - 7,8 - 二羟基 - 9,10 - 环氧 - 7,8,9,10 - 四氢BaP（BPDE）DNA加合物的形成增加了约2倍，并使反式 - 顺式 - BPDE - DNA加合物的比例提高了1.6至2.9倍。邻苯二酚处理增加了[3H]BaP涂抹后与表皮蛋白相关的放射性。由于邻苯二酚增加了3 - 羟基BaP的水平，我们考虑了3 - 羟基BaP可能增强BaP或BPDE在小鼠皮肤中的肿瘤启动活性的可能性；一项生物测定表明情况并非如此。这项研究的结果表明，邻苯二酚与其助致癌性相关的一个重要作用是其增强小鼠皮肤中反式 - BPDE - DNA加合物形成的能力。
