Sanyal M K, Li Y L, Biggers W J, Satish J, Barnea E R
Department of Obstetrics and Gynecology, Yale University Medical School, New Haven, CT.
Am J Obstet Gynecol. 1993 May;168(5):1587-97. doi: 10.1016/s0002-9378(11)90803-5.
Polynuclear aromatic hydrocarbons are important components of cigarette smoke. The toxicity of polynuclear hydrocarbons depends on their metabolic biotransformation by tissues. This study was performed to assess the effects of cigarette smoke exposure on polynuclear aromatic hydrocarbon metabolism in the human placental tissues of first-trimester pregnancy.
The expression of essential enzymes that metabolize polynuclear aromatic hydrocarbons and regulate toxic metabolism, aryl hydrocarbon hydroxylase, epoxide hydrolase, and glutathione S-transferase, were determined by immunocytochemical staining of the specific enzymes in first-trimester placental samples from both smoker and nonsmoker donors. The overall polynuclear aromatic hydrocarbon metabolism by such tissues was quantitated by a radiometric assay with benzo[a]pyrene substrate in placental villi tissues and also in isolated trophoblast cells or in cultured trophoblast cells in the presence of polynuclear aromatic hydrocarbon agent.
Immunocytochemical staining revealed that aryl hydrocarbon hydroxylase was localized on trophoblast cells of first-trimester placentas from smoker donors. Epoxide hydrolase was present in stromal and trophoblast cells, and glutathione S-transferase (pi) was present in trophoblast cells of both nonsmoker and smoker subjects. In addition, the overall metabolism of polynuclear aromatic hydrocarbon xenobiotics in such tissues (8 to 11 weeks) of donors who smoked cigarettes was observed to be increased compared with that of nonsmokers by radiometric assay of metabolic products. The increased polynuclear aromatic hydrocarbon metabolism from such exposure was also shown in isolated and purified trophoblast cells of first-trimester placental villi and in culture of such trophoblast cells of nonsmoker donors with polynuclear aromatic hydrocarbon by the same assay procedure.
Therefore, contrary to previous assumptions, these data demonstrate that cigarette smoke exposure increases the polynuclear aromatic hydrocarbon metabolism of placentas even during the early stages of pregnancy. Augmented polynuclear aromatic hydrocarbon metabolism may produce genotoxic metabolites deleterious to conceptus development.
多环芳烃是香烟烟雾的重要成分。多环烃的毒性取决于它们在组织中的代谢生物转化。本研究旨在评估香烟烟雾暴露对孕早期人胎盘组织中多环芳烃代谢的影响。
通过对吸烟者和非吸烟者捐赠者的孕早期胎盘样本中特定酶进行免疫细胞化学染色，测定代谢多环芳烃并调节毒性代谢的关键酶芳烃羟化酶、环氧化物水解酶和谷胱甘肽S-转移酶的表达。通过在胎盘绒毛组织中以及在存在多环芳烃试剂的情况下对分离的滋养层细胞或培养的滋养层细胞中使用苯并[a]芘底物进行放射性测定，对这些组织的整体多环芳烃代谢进行定量。
免疫细胞化学染色显示，芳烃羟化酶定位于吸烟者捐赠者的孕早期胎盘的滋养层细胞上。环氧化物水解酶存在于基质和滋养层细胞中，谷胱甘肽S-转移酶（pi）存在于非吸烟者和吸烟者的滋养层细胞中。此外，通过代谢产物的放射性测定观察到，吸烟者捐赠者此类组织（8至11周）中多环芳烃外源性物质的整体代谢与非吸烟者相比有所增加。通过相同的测定程序，在孕早期胎盘绒毛的分离和纯化的滋养层细胞中以及在非吸烟者捐赠者的此类滋养层细胞与多环芳烃的培养中，也显示出此类暴露导致的多环芳烃代谢增加。
因此，与先前的假设相反，这些数据表明，即使在怀孕早期，香烟烟雾暴露也会增加胎盘的多环芳烃代谢。多环芳烃代谢的增强可能会产生对胚胎发育有害的遗传毒性代谢物。
