Detection of benzo[a]pyrene-DNA adducts in human placenta and umbilical cord blood.

Placenta constitutes a vital organ of exchange between mother and foetus. In addition to this favourable effect for foetal development, placenta indirectly may allow transfer of several maternal blood xenobiotics. Human placenta and umbilical cord blood are interesting models for investigating maternal environment and the metabolism, the bioactivation and the transfer of carcinogens such as polycyclic aromatic hydrocarbons. We used them to assess the effect of a woman's smoking on the foetus. Few studies cover this subject. In pregnant women who have continued to smoke, benzo[a]pyrene compound of cigarette smoke is metabolically activated to diol-epoxide derivative: benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide, ultimate carcinogen (BPDE-I). This derivative is covalently fixed on DNA and gives BPDE-I-DNA adducts. By a competitive immunoassay technique, we determined BDPE-I-DNA adducts in 20 samples of placenta and umbilical cord blood from women who smoked (n = 15) and who did not (n = 10). Tobacco consumption was checked by urinary cotinine determination. In the group of smokers levels of adducts were found in 13 specimens of placenta (from 10 to 60 fmol/50 micrograms of DNA) and 12 umbilical cord blood (from 10 to 22.15 fmol/50 micrograms of DNA) samples. These results indicate that a mother's tobacco consumption is linked to the accumulation of BPDE-I-DNA adducts in the placenta, which are seen in smaller quantities in the umbilical cord blood, probably because of the metabolic capacity of the placenta and the transfer of B[a]P from the mother to the foetus.

Biological monitoring exposure of workers from plant producing carbon electrodes: quantification of benzo[a]pyrene DNA-adducts in leukocytes, by a 32P-postlabelling method and an immunoassay.

The levels of benzo[a]pyrene were monitored for blood DNA-benzo[a]pyrene adducts in 17 workers from a plant producing carbon electrodes, with high exposure to benzo[a]pyrene (575-902-1149 ng m(-3)). Two different techniques, a 32P-postlabelling method and a competitive immunoassay using polyclonal antibodies obtained from rabbits immunised with DNA modified by benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide were used. For each worker, urinary 1-hydroxypyrene, a potential indicator of exposure to polycyclic aromatic hydrocarbons, was measured. The effect of tobacco by urinary cotinine measurement was also considered. The postlabelling and immunoassay detection limits for DNA-benzo[a]pyrene adducts were respectively 0.15 and 10 fmol 50 microg(-1) of DNA. The results obtained by the two methods demonstrated a good detection of DNA-benzo[a]pyrene adducts, but no direct relationship between the quantity of adducts and the concentration of benzo[a]pyrene in air-borne was noted in the studied plant. The levels of DNA-benzo[a]pyrene adducts obtained by immunoassay were significantly higher than those obtained by the 32P-postlabelling (P < 0.001). For several workers, variations due to professional or non professional factors must be taken into account in interpreting the results. In conclusion, the two methods used proved very efficient in determining DNA-benzo[a]pyrene adducts, and may be useful in monitoring human exposure to known and previously unidentified environmental genotoxic agents.

Detection of benzo[a]pyrene-DNA adducts in leukocytes of coke oven workers.

Coke oven workers are often heavily exposed to polynuclear aromatic hydrocarbons (PAHs) and particularly to benzo[a]pyrene (B[a]P), which has been associated with a high incidence of cancer. B[a]P is metabolically activated to its diol-epoxide derivative, benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE-I), a potent carcinogen which binds covalently to DNA, thereby producing BPDE-I-DNA adducts. In this study, an investigation was made of the exposure of coke oven workers to PAH via the measurement of urinary 1-hydroxypyrene (1-OHP) levels, and of exposure to B[a]P by the analysis of BPDE-I-DNA adducts in leukocytes using an ELISA competitive immunoassay. 1-OHP levels measured in post-shift samples correlated with those of DNA adducts detected in leukocytes, with a mean value (140.11 fM/50 micrograms of DNA) which differed significantly from the control value (P < 0.001). It is concluded that measurement of BPDE-I-DNA adduct levels in coke plant workers is essential in determining cancer risk due to high exposure to PAHs, and in particular of B[a]P.

[Low-density lipoprotein cholesterol levels in hypercholesterolemic rabbits with or without carbon monoxide poisoning]. / Teneur en cholestérol des lipoprotéines légères chez le lapin hypercholestérolémique intoxiqué ou non par l'oxyde de carbone.

Low-density lipoproteins isolated by a selective precipitation procedure have been investigated in cholesterol-fed rabbits exposed or not to carbon monoxide. The main findings are a higher increase of their cholesterol content and cholesterol to phospholipid molar ratio without a modification in lecithin-cholesterol-acyltransferase activity in intoxicated animals. Thus, the aggravating effect of carbon monoxide exposure on the atherogenic properties of these lipoproteins could accelerate the development of atherosclerosis in cholesterol-fed rabbits.

Detection of benzo[a]pyrene-DNA adducts from leukocytes from heavy smokers.

Benzo[a]pyrene is a cigarette smoke component that is metabolized in the human body to the diol-epoxide derivative benzo[a]pyrene-trans- 7,8-dihydrodiol-9,10-epoxide (BPDE-I), which is the final carcinogen. BPDE-I binds covalently to DNA, producing BPDE-I-DNA adducts. A competitive immunoenzymetric assay was used to measure BPDE-I-DNA adducts in blood samples from 58 heavy smokers, 32 men and 26 women, attending a smoking cessation clinic. Cigarette consumption was evaluated based on urinary continine levels. None of the subjects worked in jobs involving exposure to polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene). Concentrations of BPDE-I-DNA adducts varied with cigarette consumption, ranging from 10.00 to 28.20 fmol/50 micrograms of DNA.