Ovarian susceptibility to benzo[a]pyrene: tissue burden of metabolites and DNA adducts in F-344 rats.
Ovarian susceptibility to benzo[a]pyrene: tissue burden of metabolites and DNA adducts in F-344 rats.
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DOI：
10.1080/15287394.2010.514225
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Niaz MS
中科院分区：
文献类型：
--
作者：
Ramesh A;Archibong AE;Niaz MS
暴露于环境毒物已被认为是哺乳动物不育的原因之一。本研究的目的是确定苯并[a]芘（BaP）的摄入量，这是一种环境毒物，在单次急性暴露后到达生殖组织（内部剂量）。为此，BaP反应代谢物和BaP-DNA加合物的浓度进行了测量，在整个过程中的BaP的居留在体内。对体重约220 g的10周龄雌性Fischer-344大鼠经口给予5 mg BaP/kg体重。染毒后1、7、14、2、1和28 d，采用液-液萃取法从血浆、卵巢和肝组织中提取BaP母体化合物和代谢产物。提取物进行了分析，通过反相高效液相色谱法（HPLC）。提取DNA，用~（32）P后标记法分析BaP诱导的DNA加合物。血浆、卵巢和肝脏中的BaP总代谢物浓度从第1天到第28天逐渐下降。给药组卵巢和肝组织中BaP-DNA加合物浓度显示出与代谢物相似的趋势。与肝脏相比，卵巢显示出更高浓度的DNA加合物。然而，随着暴露停止后时间的增加，肝组织中的加合物浓度开始迅速下降，从第1天到第28天。对于卵巢，加合物浓度表现出显着下降，从第1天到第7天，此后逐渐下降。BaP反应性代谢物水平和加合物浓度之间的一致性表明，反应性代谢物的生物利用度决定了与DNA的结合，从而决定了加合物在急性暴露方案中的形成和持久性。
Exposure to environmental toxicants has been implicated as one of the causative factors for infertility in mammals. The objective of this study was to determine the amount of ingested benzo[a]pyrene (BaP), an environmental toxicant that reaches the reproductive tissues (internal dose) subsequent to a single acute exposure. Toward this end, the concentrations of BaP reactive metabolites and BaP–DNA adducts were measured throughout the course of BaP’s residence in the body. Ten-week-old female Fischer-344 rats weighing approximately 220 g were administered 5 mg BaP/kg body weight orally. 1, 7, 14, 2,1 and 28 d post BaP exposure, BaP parent compound and metabolites from plasma, ovaries, and liver tissues were extracted using liquid–liquid extraction. The extracts were analyzed by reverse-phase highperformance liquid chromatography (HPLC). DNA was isolated and analyzed for BaP-induced DNA adducts by 32P-postlabeling method. The BaP total metabolite concentrations in plasma, ovaries, and liver showed a gradual decrease from d 1 to 28 post BaP administration. The BaP–DNA adducts concentrations in ovaries and liver tissues from the treatment group demonstrated a trend similar to that observed for metabolites. Ovaries showed greater concentrations of DNA adducts compared to liver. However, with an increase in time post cessation of exposure, the adduct concentrations in liver tissue started declining rapidly, from d 1 to 28. For ovaries, the adduct concentrations demonstrated a significant decline from d 1 to 7 and a gradual fall thereafter. A concordance between BaP reactive metabolite levels and adduct concentrations indicates that the bioavailability of reactive metabolites determines the binding with DNA and consequently the formation and persistence of adducts in an acute exposure regimen.
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影响因子：
4.7
作者：
GINSBERG, GL;ATHERHOLT, TB
通讯作者：
ATHERHOLT, TB
影响因子：
4.3
作者：
DEVOS, RH;VANDOKKUM, W;DEJONGBERKHOUT, P
通讯作者：
DEJONGBERKHOUT, P
影响因子：
2
作者：
Falcó, G;Domingo, JL;Müller, L
通讯作者：
Müller, L
影响因子：
5.3
作者：
BOERRIGTER, METI;WEI, JY;VIJG, J
通讯作者：
VIJG, J
影响因子：
3.5
作者：
GRIMMER, G;NAUJACK, KW;DETTBARN, G
通讯作者：
DETTBARN, G