Sanyal Mrinal K, Li You Lan
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University Medical School, New Haven, Connecticut, USA.
Birth Defects Res B Dev Reprod Toxicol. 2007 Feb;80(1):49-56. doi: 10.1002/bdrb.20102.
Generation of different metabolites and DNA-adduct(s) of metabolites of benzo[alpha]pyrene (B[alpha]P) in vitro by placental tissues (microsomes) of mothers who actively smoked cigarettes (tobacco) and those who did not smoke were analyzed to determine the variability in metabolism of the B[alpha]P substrate among individual placental samples.
Overall B[alpha]P metabolism was assayed by alkaline aqueous extraction of metabolites, and reactive metabolites by DNA adducts of B[alpha]P-metabolites produced by salmon sperm DNA added to the incubation mixtures of the substrate and microsomes of exposed- and unexposed-placentas to maternal cigarette smoke. Array of B[alpha]P-metabolites produced by the same incubations were identified by high pressure liquid chromatography of the aqueous extracts.
Subsets of smoke-exposed placentas assessed by cluster analysis had augmented metabolic activity, others did not respond to smoke exposure. CYP1A1 expression in trophoblast cells analyzed by immunohistochemistry did not correlate with smoke exposure. The DNA-adducts generated was variable, regardless of verbally reported levels of maternal exposure. The amounts of different B[alpha]P-metabolites produced by individual samples matched for similar levels of exposure during pregnancy by self-reported smoking (1 pack/day) were also not comparable. Metabolism of B[alpha]P into different metabolites, and production of toxic DNA adducts from metabolites in vitro by human placenta were variable and unrelated to the extent of smoke exposure.
The metabolic characteristic of human placenta for xenobiotic exposure substrates is based on the expression and function of diverse enzymes, and such metabolism exhibited inter-individual variation for toxic metabolite production or detoxification of the substrates in response to maternal smoke exposure.
分析主动吸烟（烟草）和不吸烟母亲的胎盘组织（微粒体）在体外对苯并[a]芘（B[a]P）代谢产物及DNA加合物的生成情况，以确定个体胎盘样本中B[a]P底物代谢的变异性。
通过碱性水萃取代谢产物来测定总体B[a]P代谢，通过将鲑鱼精子DNA与暴露于和未暴露于母体香烟烟雾的胎盘底物及微粒体的孵育混合物中产生的B[a]P代谢产物的DNA加合物来测定反应性代谢产物。通过对水提取物进行高压液相色谱法鉴定相同孵育产生的B[a]P代谢产物阵列。
通过聚类分析评估的暴露于烟雾的胎盘亚组具有增强的代谢活性，其他亚组对烟雾暴露无反应。通过免疫组织化学分析的滋养层细胞中CYP1A1表达与烟雾暴露无关。无论母体暴露的口头报告水平如何，产生的DNA加合物都是可变的。个体样本在孕期通过自我报告吸烟（每天1包）匹配相似暴露水平时产生 的不同B[a]P代谢产物的量也不可比。人胎盘在体外将B[a]P代谢为不同代谢产物以及从代谢产物产生有毒DNA加合物的过程是可变的，且与烟雾暴露程度无关。
人胎盘对外源性暴露底物的代谢特征基于多种酶的表达和功能，并且这种代谢在有毒代谢产物的产生或底物解毒以响应母体烟雾暴露方面表现出个体间差异。
