Bioactivation of Polycyclic Aromatic Hydrocarbon Carcinogens within the vascular Wall: Implications for Human Atherogenesis

@article{Ramos2005BioactivationOP,
  title={Bioactivation of Polycyclic Aromatic Hydrocarbon Carcinogens within the vascular Wall: Implications for Human Atherogenesis},
  author={Kenneth S. Ramos and Bhagavatula Moorthy},
  journal={Drug Metabolism Reviews},
  year={2005},
  volume={37},
  pages={595 - 610}
}
Atherogenesis is a complex pathogenetic process involving a variety of structural and functional deficits within the arterial wall that culminate in the formation of fibrous atherosclerotic plaques. Cigarette smoking is potentially the most remediable contributor to cardiovascular mortality and morbidity. Among the 4000 plus chemicals present in tobacco and tobacco smoke, polycyclic aromatic hydrocarbons (PAHs) have been firmly implicated in the etiology of atherosclerosis in experimental model… Expand
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References

SHOWING 1-10 OF 85 REFERENCES
IMPACT OF CELLULAR METABOLISM ON THE BIOLOGICAL EFFECTS OF BENZO[A]PYRENE AND RELATED HYDROCARBONS†
TLDR
This review summarizes recent advances in the understanding of biological mechanisms of BaP toxicity at the molecular level, and the role of metabolic intermediates in carcinogenesis, atherogenesis, and teratogenesis. Expand
Aryl 4-monooxygenase and cytochrome P-450 in the aorta: possible role in atherosclerosis.
  • M. Juchau, J. Bond, E. Benditt
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1976
TLDR
The monooxygenase activity found in the aorta could play a significant role in the etiology and pathogenesis of atherosclerosis in humans by catalyzing the conversion of environmental promutagens to mutagenic initiators and/or cytotoxic factors, thus leading to development of benign, smooth muscle tumors of the inner lining of artery walls. Expand
Modulation of protooncogene expression in rat aortic smooth muscle cells by benzo[a]pyrene.
TLDR
It is shown that BaP enhances serum-induced protooncogene expression during the early part of the cell cycle in rat aortic SMCs and suggest that binding of BaP to intracellular proteins may play a role in these responses. Expand
DNA adducts and human atherosclerotic lesions.
TLDR
The induction of DNA adducts suggests that alterations at the DNA level may contribute to the development of atherosclerosis, which may share a similar etiology, i.e. genotoxic action of environmental chemicals. Expand
Activation of c-Ha-ras by benzo(a)pyrene in vascular smooth muscle cells involves redox stress and aryl hydrocarbon receptor.
TLDR
BaP did not enhance c-Ha-ras expression in vSMCs from AhR knockout mice, although aryl hydrocarbon hydroxylase activity was constitutively expressed in these cells, suggesting that c- Ha-ras activation by BaP involves a redox-sensitive mechanism that is coupled to AhR receptor-dependent functions. Expand
DNA adducts and chronic degenerative disease. Pathogenetic relevance and implications in preventive medicine.
TLDR
In this article, particular emphasis is given to molecular alterations in the heart, which is the preferential target for the formation of DNA adducts in smokers, and in human aorta, where an extensive molecular epidemiology project is documenting the systematic presence ofAdducts to the nuclear DNA of smooth muscle cells from atherosclerotic lesions, and their significant correlation with known atherogenic risk factors. Expand
Arteriosclerotic plaque development is 'promoted' by polynuclear aromatic hydrocarbons.
TLDR
There was a poor correlation between mutagenicity or carcinogenicity and plaque 'promotion', which may reflect a role for different metabolites in these processes. Expand
Induction of cytochrome CYPIA1 and formation of toxic metabolites of benzo[a]pyrene by rat aorta: a possible role in atherogenesis.
TLDR
The data suggest that the aortas of induced animals metabolize the BaP in cigarette smoke to carcinogenic and toxic products and that this metabolism may initiate vessel injury and lead to the accelerated atherosclerosis seen in cigarette smokers. Expand
The atherogen 3-methylcholanthrene induces multiple DNA adducts in mouse aortic smooth muscle cells: role of cytochrome P4501B1.
TLDR
The induction of high levels of multiple DNA adducts in SMCs by MC suggests that SMCs have a functional enzymatic machinery capable of metabolically activating MC to genotoxic metabolites that may play a role in the induction of atherosclerosis by MC. Expand
Carcinogenesis and atherogenesis: differences in monooxygenase inducibility and bioactivation of benzo[a]pyrene in aortic and hepatic tissues of atherosclerosis-susceptible versus resistant pigeons.
TLDR
It is suggested that these pigeon strains might offer a promising system in which to further study the role of target tissue biotransformation in the atherogenic actions of polynuclear aromatic hydrocarbons. Expand
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