Polycyclic Aromatic Hydrocarbon-Induced Carcinogenesis – An Introduction

Luch, Andreas

doi:10.1142/9781860949333_0001

Cited by 15 publications

(7 citation statements)

References 39 publications

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“…The increased coal burning in China, often without strict emission controls, has been associated with recent increases in lung diseases in that country (Mumford et al, 1995; Watts, 2006; Yu et al, 2006). However, even though PAHs are released from burning of organic material, most of the human exposure to these pollutants is dietary (Luch, 2005). …”

Section: Ultra-low Dose Cancer Study With the Polycyclic Aromatic Hydmentioning

confidence: 99%

Rainbow trout (Oncorhynchus mykiss) and ultra-low dose cancer studies

Williams

Orner

et al. 2009

Comparative Biochemistry and Physiology Part C: Toxicology &

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Cancer risk assessment utilizing rodents requires extrapolation across five orders of magnitude to estimate the Virtually Safe Dose (VSD). Regulatory agencies rely upon the Linear Extrapolated Dose (LED) except when sufficient information on mechanism of action justifies alternative models. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptComp Biochem Physiol C Toxicol Pharmacol. Author manuscript; available in PMC 2010 July 1. Published in final edited form as:Comp human cancer for forty years. Low cost and high capacity, made possible by our unique facility, along with low spontaneous background and high sensitivity, allow design and conduct of statistically challenging studies not possible in rodents. Utilization of custom microarrays demonstrates similarities in gene expression in trout and human hepatocellular carcinoma (HCC). We have completed one study employing over 42,000 trout with dibenzo[a,l]pyrene (DBP) and determined the dose resulting in 1 additional cancer in 5,000 animals, a 50-fold enhancement over the mouse ED01 study. Liver tumor incidence at low dose deviated significantly from linearity (concave down), whereas, DBP-DNA adductions deviated slightly (convex up). A second study is underway with aflatoxin B 1 (AFB 1 ). Results to date indicate AFB 1 at low dose, in contrast to DBP, elicits a linear dose-response function on the log-log scale which falls below the LED with a slope slightly greater than 1.0. Such studies demonstrate the statistical power of the trout cancer model and strengthen the case for incorporation of these data-sets into risk assessment for these environmental human carcinogens.

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Section: Ultra-low Dose Cancer Study With the Polycyclic Aromatic Hydmentioning

confidence: 99%

Rainbow trout (Oncorhynchus mykiss) and ultra-low dose cancer studies

Williams

Orner

et al. 2009

Comparative Biochemistry and Physiology Part C: Toxicology &

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“…Polycyclic aromatic hydrocarbons (PAHs) are a large class of compounds mainly formed by the incomplete combustion of organic matter. They are commonly found in polluted air and water, tobacco smoke, broiled and smoked foods, and in certain occupational environments such as coke production from coal and other processes involving soot and tar − . Humans readily absorb PAH into the body through the lung, gastrointestinal tract, and skin.…”

Section: Introductionmentioning

confidence: 99%

Analysis of r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene in Human Urine: A Biomarker for Directly Assessing Carcinogenic Polycyclic Aromatic Hydrocarbon Exposure Plus Metabolic Activation

Zhong

Carmella

Hochalter

et al. 2010

Chem. Res. Toxicol.

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Polycyclic aromatic hydrocarbons (PAH) are believed to be causative agents for various types of cancers in humans. Benzo[a]pyrene (BaP) is a prototypic carcinogenic PAH, which requires metabolic activation to elicit its detrimental effects. The major end product of its diol epoxide metabolic activation pathway is r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (trans, anti-BaPT). Individual differences in exposure to, and metabolic activation of, carcinogenic PAH may influence cancer risk. Measurement of PAH metabolites in human urine could provide a direct way to assess individual differences in susceptibility to PAH-related cancer. In this paper, we describe a sensitive and reliable method for quantitation of trans, anti-BaPT in human urine using gas chromatography-negative ion chemical ionization-tandem mass spectrometry (GC-NICI-MS/MS). [13C6] trans, anti-BaPT was used as the internal standard. The urine was treated with β-glucuronidase and sulfatase, and then trans, anti-BaPT was enriched by solid-phase extraction with polymeric reversed phase and phenylboronic acid cartridges. The sample was silylated and analyzed by GC-NICI-MS/MS with selected reaction monitoring (SRM) for the trimethylsilyl (TMS) derivatives of trans, anti-BaPT (m/z 446→ m/z 255) and [13C6]trans, anti-BaPT (m/z 452→ m/z 261). The mean assay recovery was 44%. The instrumental on-column detection limit was about 20 amol of trans, anti-BaPT (as BaPT-TMS). trans, anti-BaPT was readily detected in all urine samples analyzed including 30 smokers (0.71 ± 0.64 fmol/mg creatinine) and 30 non-smokers (0.34 ± 0.2 fmol/mg creatinine) (P = 0.0018). The results of this study demonstrate a highly sensitive and selective method for quantitation of trans, anti-BaPT in human urine. This is to our knowledge the first study to show that smokers have significantly higher levels of trans, anti-BaPT in their urine than do non-smokers. This method may be useful as a direct phenotyping approach to assess individual differences in uptake and metabolic activation of carcinogenic PAH.

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“…PAHs are formed from the incomplete combustion of organic materials including the burning of coal, petroleum products or tobacco (reviewed in ref. 39) and have been listed as human carcinogens by international agency for research on cancer (40). Increasing energy requirements, especially in countries such as China, are resulting in greater use of coal for energy production; indeed, China derives 70% of its energy from burning coal and the consumption is greater than the USA, European Union and Japan combined (41,42,43,44).…”

Section: Discussionmentioning

confidence: 99%

Identifying efficacious approaches to chemoprevention with chlorophyllin, purified chlorophylls and freeze-dried spinach in a mouse model of transplacental carcinogenesis

Castro

Löhr

Fischer³

et al. 2008

Carcinogenesis

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The carcinogenic potential of dibenzo[a,l]pyrene (DBP) has been well characterized in numerous animal models. We have previously documented that a single dose of 15 mg/Kg DBP to pregnant mice late in gestation (GD 17) produces an aggressive T-cell lymphoma as well as lung and liver cancer in offspring. The current study examines the chemopreventative properties of chlorophyllin (CHL) and chlorophyll (Chl) in this transplacental carcinogenesis model. Pregnant B6129SF1 females, bred to 129S1/SvIm males, received purified diets incorporated with either 2000 p.p.m. CHL, 2000 p.p.m. Chl or 10% freeze-dried spinach beginning at gestation day 9. Lymphoma-dependent mortality was not significantly altered by maternal consumption of any of the diet and little effect on lung tumor burden in mice surviving to 10 months of age was observed. However, coadministration of CHL at 380 mg/Kg with DBP by gavage (molar ratio of 10:1, CHL:DBP) provided significant protection against DBP-initiated carcinogenesis. Offspring born to dams receiving CHL co-gavaged with DBP exhibited markedly less lymphoma-dependent mortality (P < 0.001). The degree of protection by CHL, compared with controls dosed with DBP in tricaprylin (TCP) as the vehicle, was less marked, but still significant. Coadministration of CHL (TCP as vehicle) also reduced lung tumor multiplicity in mice by approximately 50% and this was observed throughout the study (P < 0.005). This is the first demonstration that CHL can provide potent chemoprotection in a transplacental carcinogenesis model and support a mechanism involving complex-mediated reduction of carcinogen uptake.

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Polycyclic Aromatic Hydrocarbon-Induced Carcinogenesis – An Introduction

Cited by 15 publications

References 39 publications

Rainbow trout (Oncorhynchus mykiss) and ultra-low dose cancer studies

Rainbow trout (Oncorhynchus mykiss) and ultra-low dose cancer studies

Analysis of r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene in Human Urine: A Biomarker for Directly Assessing Carcinogenic Polycyclic Aromatic Hydrocarbon Exposure Plus Metabolic Activation

Identifying efficacious approaches to chemoprevention with chlorophyllin, purified chlorophylls and freeze-dried spinach in a mouse model of transplacental carcinogenesis

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