Augmentation of polynuclear aromatic hydrocarbon metabolism of human placental tissues of first-trimester pregnancy by cigarette smoke exposure

Abstract

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.