Formation of benzo[a]pyrene and 7,12‐dimethylbenz[a]anthracene adducts in vascular endothelia of cytochrome P4501A–induced chicken embryos

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and birds may be exposed to PAHs via diet, from preening feathers contaminated with oil, or through contamination of the eggshell during embryo development. In the present study, tissue distribution and the cell-specific binding of two labeled PAHs, benzo[a]pyrene ([3H]BaP) and 7,12-dimethylbenz[a]anthracene ([3H]DMBA), were examined in chicken embryos exposed in ovo to CYP1A inducers. Tape-section autoradiograms revealed high concentrations of radioactivity in the bile, liver, kidneys, heart, and leptomeninges. Light microscopy autoradiography of solvent-extracted tissue slices showed a high and selective binding in endothelial cells in certain blood vessels in brain, heart, lung, and chest muscle. Binding was also observed in blood vessel endothelial cells in the chorioallantoic membrane (CAM), an extraembryonal tissue lining the eggshell. Endothelial binding was confirmed in CAM exposed in vitro, implying that tissue-binding metabolites were formed in situ. The CYP1A inhibitor ellipticine abolished bleeding in the target endothelial cells in CAM. It is thus concluded that blood vessel endothelia in various tissues in birds can bioactivate environmental contaminants and be targets for their toxicity. In view of its critical position beneath the shell, the CAM could be an important target for toxicants following external exposure in oviparous species.

17 ?-estradiol and not genistein modulateslacI mutant frequency and types of mutation induced in the heart of ovariectomized big blue rats treated with 7, 12-dimethylbenz[a]anthracene

“…The most common DMBA-induced mutations in control diet rats were A:T?T:A transversions (42%), followed by G:C?T:A transversions (19%), which are consistent with the abundance of DMBA-dA and DMBAdG adducts observed in the mammary gland, a target tissue for DMBA carcinogenicity in the rat . Although DMBA-induced DNA adducts in the heart were neither measured nor characterized in the present study, DNA-adduct formation has been reported in the heart and vascular endothelia of rodents and birds exposed to DMBA [Wang and Su, 2001;Granberg et al, 2003]. These results and ours suggest that DMBA forms adducts in the heart that lead to gene mutations.…”

Activation of group IVC phospholipase A2 by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells

“…Treatment of mice with benzo(a)pyrene (B[a]P) or dimethylbenzanthracene induces bioactivation of drug-metabolizing enzymes and irreversible binding of hydrocarbon metabolites to endothelial cells (EC). These data suggest that PAHs may augment atherosclerosis by a process that involves EC damage (Granberg et al 2003), possibly via apoptosis. The importance of apoptotic cell death to the atherosclerotic process is well documented (Dimmeler et al 1998; Geng and Libby 1995; Isner et al 1995).…”

The Aryl Hydrocarbon Receptor: A Key Bridging Molecule of External and Internal Chemical Signals

“…In ovo studies showed that the bile, liver, kidneys, heart, and leptomeninges were the most contaminated organs of chicken embryos exposed to PAHs; in part, the bioactivity of the PAHs in these tissues was facilitated by the formation of PAH adducts in blood vessel endothelium. 133 In chickens hatched from the PCB-126 exposed eggs, expression levels of Cyp1a4 mRNA in whole liver tissue increased 29-fold. 134 Damage to hepatic membrane structure and function was correlated with the increased mortality in chicken embryos exposed to PCB-126.…”