Population distribution of placental benzo(α)pyrene metabolism in smokers

Abstract

Human placental microsomes isolated from term placentas derived from nonsmoking women and women smoking 1 to 40 cigarettes a day were analyzed for the metabolism of benzo(a)pyrene measured as various metabolites by HPLC and/or as aryl hydrocarbon hydroxylase (AHH)6 activity. In accordance with other reports, AHH activity was several times higher in smokers than in nonsmokers. Regression analysis on 13 different placental tissues from women smoking from 1 to 40 cigarettes demonstrated a high correlation (r = 0.8 to 0.9) between AHH activity (or the formation of benzo(a)pyrene phenols resolved by HPLC) versus the formation of the procarcinogenic benzo(a)pyrene-7,8-diol. Subsequent studies on placentas derived from 67 women who smoked 10 to 40 cigarettes per day demonstrated a definite dose-response relationship between AHH activity and the number of cigarettes smoked/day. The dose-response curve was sigmoidal in shape; however, when the data were plotted on a semi-log scale the curve assumed a linear shape, reaching saturation of AHH induction beyond 20 to 25 cigarettes/day. While mean AHH activity was dependent upon the number of cigarettes smoked/day, considerable interindividual variability in AHH (ranging more than 1,000-fold in some cases) was observed among individuals with comparable smoking histories, i.e. smoking the same number of cigarettes. Population distribution suggested clustering of the population in the low-AHH-activity region while cord-blood thiocyanate analysis and twin studies suggested that genetic factors contributed to a major portion of the inter-individual variability in AHH activity observed among smokers.

Is aryl hydrocarbon hydroxylase activity a new prognostic indicator for breast cancer?

“…Large interindividual variations in AHH activities were also found in other human extrahepatic tissues, such as lung (Cohen et al, 1979;Sabadie et al, 1981;Roberts et al, 1986), lymphocytes (Kellerman et al, 1973) and placenta (Gurtoo et al, 1983 Our main result, which is that high AHH activity in breast cancer tissue predicts a bad prognosis of the disease, is a new one. The AHH activity of benign tumours was significantly lower than that in carcinomas and cancers with good prognosis lower than that of bad prognosis (though there were many individual exceptions).…”

Xenobiotic Metabolism in the Maternal-Placental-Fetal Unit: Implications for Fetal Toxicity

“…We would like to measure the extent of genotoxic damage to placental DNA and correlate it with the biological outcome, be it new born well-being and characteristics, placental status and hormone produc tion, child development and so on. If the inducibility of placental AHH activity by maternal cigarette smoking is under genetic control, as it seems to be [13,14], we should be able to detect 'risk pregnancies' with respect to polycyclic aromatic hydrocarbons.…”

Transport of Benzo[α]pyrene in the Dually Perfused Human Placenta Perfusion Model: Effect of Albumin in the Perfusion Medium

“…blood, as had Autrup et al [11,33]. It should also be noted that BPDE is not the only metabolite of BaP [34], and that besides its pro-carcinogenicity, BaP can cause aryl hydrocarbon receptor (AhR) pathway-related abnormalities in placental vasculature and intrauterine growth restriction in C57B1/6 mice [35] and neurodevelopmental effects in LongEvans rats [36].…”