Question

Gonna Test Something Real Fast... Dont Mind me, I'll delete question @mods

Answer 1

\[\begin{document}
\title{Polycyclic Aromatic Hydrocarbons:\\ Benzo[b]fluoranthene and Carcinogenesis}
\author{Alan JQ Greene, AA\thanks{The author would like to thank Professor Christos Deligkaris, PhD, Drury University, Department of Physics for introducing him to the field of computational biophysics and small molecule-DNA interaction modeling}}
\affil{Drury University, Department of Environmental Sciences, Springfield MO\\For:\\ CHEM 0201; Professors Mark Wood, PhD and Albert Korrir, PhD}
\date{\today}
\maketitle
\begin{abstract}
This paper serves as the capstone of CHEM 0201-Environmental Chemistry. The author completed literature research of this topic and reported findings herein. The current understanding of Polycyclic Aromatic Hydrocarbons (PAHs) is vast, but still unfinished. The author explored one of these compounds, Benzo[b]fluoranthene (B[b]F) and its possible roles in carcinogenesis. This paper serves as a semi-comprehensive overview of the current scientific findings of B[b]F in carcinogenesis, areas for future study and the impact of PAHs to ecological systems and humans.
\end{abstract}
\begin{multicols}{2}
\section{Introduction}
\hspace*{26 bp}Polycyclic Aromatic Hydrocarbons (PAHs) are ubiquitous pollutants, that is: they are found in soil, air and water\textsuperscript{2,9}. They are named as such because they are composed of joined cyclic rings; thus, they tend to be of planar geometry. However, upon entering a biological system they are metabolised to more polar and multi-planar forms\textsuperscript{6}. This metabolisation is important to our understanding of the function PAHs because generally speaking, bio-important interactions do not occur without metabolisation. Additionally when biota have a method to metabolise a compound they tend to, our understanding of biota is that they favour lower entropy configurations and therefore utlize all compounds they can.\\
\hspace*{26 bp}It is thought that these metabolites of PAHs cause carcinogenesis by forming DNA-PAH complexes which then inhibit the proper use of DNA in cellular functions\textsuperscript{4,6,10}. We will explore evidence related to this hypothesis, and by doing so, examine the amounts of PAHs needed to form these adducts and thus predict possible ecological damage done by these pollutants. However, the purpose of this paper is to examine one PAH in particular, Benzo[b]fluoranthene (B[b]F), its metabolites, evidence of carcinogenesis, prevalence and possible ecological damages.
\section{Location and\\Distribution of PAHs}
\hspace*{26 bp}As mentioned, PAHs are found in all environmental substrates (air, water, and soil). The amounts and distributions of these pollutants are important to our understanding of possible ecological impacts. With the study of chimney sweeps, and their increased incidence of cancer in the 18th century, and subsequent advances in science with respect to the ability to find rationalities for this increased rate of carcinogenesis: it was concluded that the PAH Benzo[a]pyrene (B[a]P) was causing this increase\textsuperscript{6}. B[a]P, like all other PAHs, is formed from the incomplete combustion of organics. In particular B[a]P is associated with coal tar and tobacco smoke\textsuperscript{6,7,9}. Because of these formation requirements, it can be seen why these chemicals find their way to every substrate of biota, they are formed from both natural and anthropogenic methods. \\
\hspace*{26 bp}However, their distribution in the entire biosphere is not well studied, indeed only small amounts of data are available for the amounts of these chemicals in any given area. It is known that these compounds are generally insoluble in water and cannot be disbursed easily with water (rainwater for instance)\textsuperscript{6}. This being said, for our local environment a study has been done by Missouri State University for the City of Springfield to examine the exact amounts of PAHs found in soils in the area\textsuperscript{9}. When comparing this data with data used to cause carcinogenic effects in lab animals, ecological damage possibilities become clear--and are discussed in section 5.
\section{Metabolism of B[b]F}
\hspace*{26 bp}The normal metabolisation of PAHs is to form a diol-epoxide in the bay-region of the compound, and it is thought that this polar form leads to adduct formation\textsuperscript{3,6,7}. There is an issue with this for B[b]F in that studies have found that a bay-region diol-epoxide is not generally formed, and is of higher entropy than other forms that are possible\textsuperscript{1-7}. Namely, it has been found that B[b]F is first metabolised like all other PAHs to an oxide additive and then broken to a diol (B[b]F-9,10-diol for example)\textsuperscript{1,2,6,10}. However, the following step of adding an oxygen and forming a diol-epoxide which is common in other PAH is not completed; however, studies have shown that alternatives (5-OH-B[b]F-9,10-diol; 6-OH-B[b]F-9,10-diol) are formed \emph{in vivo}, and the 5-OH version of B[b]F is likely the final carcinogenic form\textsuperscript{1-8,10}. Other, more exotic metabolites have been found, but have not been linked in any real way with carcinogenesis\textsuperscript{5}. It is important to note that no B[b]F metabolisation studies have been done for humans, and all conclusions are based on \emph{in vivo} mouse systems.
\section{Carcinogenesis}
\hspace*{26 bp}While the subject of carcinogenesis is too far reaching for the purpose of this paper, it is important to note what is currently known about the subject in broad terms, in order to later examine the possible ecological damage done by PAHs. \\
\hspace*{26 bp}PAHs tend towards adduct formation, and as such we can limit the scope of this subject to small drug (ligand) and DNA interactions\textsuperscript{6}. It is understood that by binding to DNA, ligands interrupt things like helicase opening of the B-type DNA, and thus influence rates and/or ability to complete transcription and translation\textsuperscript{11,12}. Moreover, it has been shown that environmental agents tend to be the most devastating because they interact so freely with biota--whereas anthropogenic agents have to have a human to start the vector\textsuperscript{13}. Although adduct formation is most common, it is important to note that intercalation (non-covalent association between base pairs) is possible because of the planar nature of PAHs before metabolisation, and although not well studied can be carcinogenic\textsuperscript{6,11,13}.\\
\hspace*{26 bp}For B[b]F it has been found that adduct formation occurs, and nearly equal amounts of tumorgenesis occur when using B[b]F or the metabolite 5-OH-B[b]F-9,10-diol; which indicates that this is the final metabolite and is carcinogenic\textsuperscript{5,10}. It has been shown that this occurs in the Ki-\emph{ras} gene in mice, which is unlike B[a]P which occurs on TP53\textsuperscript{6,7,11}. However, current hypotheses about these adducts, and emerging statstical data indicate that the Ki-\emph{ras} gene in mice and the TP53 gene in humans may be analogous, based on the rates of adduct formation in the two\textsuperscript{7}.
\section{Ecological Damage}
\hspace*{26 bp}Although it has not been studied directly due to the difficulty of determining exposure amounts and the ubiquitous nature of PAHs: it is clear from laboratory experimentation that very small amounts of concentrated PAHs cause carcinogenesis in various animals\textsuperscript{3-8}. As more studies about the concentration of these chemicals in the environment are completed, more meaningful connections can be made. However, from looking locally at the aforementioned MSU study, it was found that in coal-tar sealant lots, an average of 262,820 $\mu\mathrm{mol/kg}$ B[b]F was found\textsuperscript{9}. When compared to studies done on B[b]F and metabolites, 0.04 $\mu\mathrm{mol}$ was enough to create statistically meaningful carcinogenesis\textsuperscript{10}. By utilizing stochiometry we can see that this labrotory dosing is equivalent to 5046 $\mu\mathrm{mol/kg}$.\\
\hspace*{26 bp}It is then clear that the amounts of these chemicals which are present in certain situations could cause significant ecological damage and human health concerns. While B[b]F is at the highest concentrations in coal-tar sealant lots, it is not a known human carcinogen by EPA standards and as such is not regulated in any real way\textsuperscript{3,9}. With increasing research in the subject, it is possible that the science will be able to show irrefutable correlations between B[b]F and human carcinogenesis leading to tighter controls by EPA as to the disbursal of it.
\section{Future Research}
\hspace*{26 bp}There are still some very important questions to be answered about B[b]F and PAHs in general; namely, what are the bio-important metabolites of PAHs that have not been well studied, where does DNA-PAH binding occur, when in the cell cycle does the binding occur, what are the effects of these adduct formations and can adduct formation be prevented or repaired? \\
\hspace*{26 bp}In the case of B[b]F, the first question has seemingly been answered\textsuperscript{1-8,10} The rest of the list is dependent on determining where exactly on the genes the binding occurs. This has not been well studied, and as previously mentioned the Ki-\emph{ras}-TP53 gene analogs are important. The author hopes to model the interactions of 5-OH-B[b]F-9,10-diol and TP53 (human) starting next semester. If meaningful data can be ascertained, it may lead to the rest of the list falling into order in rapid succession and as mentioned, adding to the evidence of human carcinogenesis, and with further biochemical study perhaps the EPA ultimately reclassifying the compound. Alternatively, data might show that the hypothesis that Ki-\emph{ras} and TP53 are cross species analogs is inaccurate, which would be equally important for the understanding of these chemicals.
\section{Conclusions}
\hspace*{26 bp}Clearly, there are still some important questions about PAHs and B[b]F, specifically, to answer. However, through the many years of research into this compound, it has been shown to be a procarcinogen in mice and other animals\textsuperscript{1-9,10-13}. Because it is formed from combustion of organics and is insoluble in water it has become ubiquitous in the environment\textsuperscript{3,6,13}. The concentrations found in the environment when compared to those that caused carcinogenesis in lab indicate that ecological damage has been done, and will continue to be done until a human health link is made; because, without it little public policy change is likely\textsuperscript{1-13}. The author's future work intends to find this connection.
\begin{thebibliography}{1}
\footnotesize
\bibitem{1}Amin, S., E. J. LaVoie, and S. S. Hecht. {\em Identification of Metabolites of Benzo[b]fluoranthene.} Carcinogenesis 3.2 (1982): 174
\bibitem{2}Baer-Dubowska, Wanda, and K. Marcinkowski. {\em Alternative Pathways of Polycyclic Aromatic Hydrocarbons Activation: The Formation of Polar DNA Adducts.} Acta Biochimica Polonica 46.2 (1999): 263-74.
\bibitem{3}{\em Benzo[b]fluoranthene (CASRN 205-99-2) | IRIS | US EPA.} EPA. Environmental Protection Agency Website
\bibitem{4}Geddie, J. E., S. Amin, K. Huie, and S. S. Hecht. {\em Formation and Tumorigenicity of Benzo[b]fluoranthene Metabolites in Mouse Epidermis.} Carcinogenesis 8.11 (1987): 1579-584.
\bibitem{5}He, Zhen Min, et al. {\em 11,12-Epoxy-9,10,11,12-tetrahydro-5,9,10-trihydroxybenzo[b]fluoranthene: Its Role in the Metabolic Activation of B[b]F in Mouse Skin.} Polycyclic Aromatic Compounds 6 (1994): 17-25.
\bibitem{6}{\em IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 92, Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures: This Publication Represents the Views and Expert Opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Which Met in Lyon, 11 - 18 October 2005.} Vol. 92. Lyon: WHO, 2010.
\bibitem{7}Jackson, Marcus A., et al. {\em Genetic Alterations in Cancer Knowledge System: Analysis of Gene Mutations in Mouse and Human Liver and Lung Tumors.} Toxicological Sciences 90.2 (2006): 400-18.
\bibitem{8}Mass, Marc J., et al. {\em Benzo[b]fluoranthene: Tumorigenicity in Strain A/J Mouse Lungs, DNA Adducts and Mutations in the Ki-ras Oncogene.} Carcinogenesis 17.8 (1996): 1701-704.
\bibitem{9}Pavlowsky, Robert T., PhD. {\em Baseline Study of PAH Sources and Concentrations in Pond and Stream Sediment, Springfield, Missouri} City of Springfield, 2012.
\bibitem{10}Weyand, Eric H., et al. {\em Detection of the Major DNA Adducts of Benzo[b]fluoranthene in Mouse Skin: Role of Phenolic Dihydrodiols.} Chemical Research in Toxicology 6 (1993): 568-77.
\bibitem{11}Luch, Andreas. {\em Nature and Nurture--Lessons From Chemical Carcinogenesis} Nature Reviews, Cancer 5 (2005): 113-125
\bibitem{12}Geacintov, Nicholas, and Suse Broyde. {\em The Chemical Biology of DNA Damage: Introduction and Prespectives on the Chemistry and Biology of DNA Damage} 2010, Wiley-VCH: 3-20
\bibitem{13}Wogan, Gerald, et al. {\em Environmental and chemical carcinogenesis} Seminars in Cancer Biology 17 (2004): 473-486.
\bibitem{auth}\textbf{The author would like to note that below this point are bibliographic references not directly cited in this paper but influenced the authorship of the paper.}
\bibitem{14}Vogelstein, Bert, and Kenneth W Kinzler.{\em Cancer genes and the pathways they control} Nature Medicine 10.8 (2004):789-799.
\bibitem{15}Benigni, Romualdo and Cecilia Bossa.{\em Mechanisms of Chemical Carcinogenicity and Mutagenicity: A Review with Implications for Predictive Toxicology} Chemical Reviews (2010): A-AD
\bibitem{16}Hanahan, Douglas and Robert A. Weinberg. {\em The Hallmarks of Cancer} Cell 100 (2000): 57-70
\bibitem{17}Stratton, Michael. {\em Expoloring the Genomes of Cancer Cells: Progress and Promise} Science 331 (2011): 1553-1558
\bibitem{18}Hecht, Stephen S. {\em Progress and Challenges in Selected Areas of Tobacco Carcinogenesis} Chemical Research in Toxicology 21 (2008): 160-171
\bibitem{19}Chen, Kai, S. James Adelstein, Amin I Kassis. {\em Molecular modeling of the interaction of iodinated Hoechest analogs with DNA: implications for new radiopharmaceutical design} Journal of Molecular Structure (Theochem) 711 (2004): 49-56
\bibitem{20}Huey, Ruth, et al. {\em Software News and Update: A Semiempirical Free Energy Force Field with Charge-Based Desolvation} Journal of Computational Chemistry 26.6 (2006): 1145-1152
\bibitem{21}Detering, Carsten and Gabriele Varani {\em Validation of Automated Docking Programs for Docking and Database Screening against RNA Drug Targets} Journal of Medical Chemistry 47 (2004): 4188-4201
\bibitem{22}Evans, David A. and Stephen Niedle. {\em Virtual Screening of DNA Minor Groove Binders} Jounral of Medical Chemistry 49 (2006): 4232-4238
\bibitem{23}Olson, Wilma K., et al. {\em A Standard Reference Frame for the Description of Nucleic Acid Base-pair Geometry} Journal of Molecular Biology 313 (2001): 229-237
\bibitem{24}Ussery, David W. {\em DNA Structure: A-, B-, and Z-DNA Helix Families} Encyclopedia of Life Sciences (2002): 1-7
\bibitem{25}Gmeiner, William H. and Bernhard J Walberer. {\em Base Pairing in DNA: Unusual Patterns} Encyclopedia of Life Sciences (2001): 1-10
\bibitem{26}Berman, Helen M. {\em Crystal Studies of B-DNA: The Answers and the Questions} Biopolymers 44 (1997) 23-44
\bibitem{27}Westhof, Eric. {\em Water: An Integral Part of Nucleic Acid Structure} Annual Review of Biophysics and Biophysical Chemistry 17 (1988): 125-144
\bibitem{28}Lu, Xiang-Jun and Wilma K Olson. {\em 3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures} Nature Protocols 3.7 (2008): 1213-1227
\bibitem{29}Doetsch, Paul W. {\em DNA Damage} Encyclopedia of Life Sciences (2001): 1-7
\bibitem{30}Friedberg, Errorl C. {\em DNA damage and repair} Nature 421.23 (2003): 436-440
\bibitem{31}Hoeijmakers, Jan H.J. {\em DNA Damage, Aging, and Cancer} New England Journal of Medicine 361.15 (2009): 1475-1485
\\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\\\ \\
\end{thebibliography}
\end{multicols}
\end{document}\]

Answer 2

hehe tex doesnt work here u know

Answer 3

also there is a section dedicated to latex practice :)

Answer 4

and you can't delete a question xD

Answer 5

\[\section{Introduction}
\hspace*{26 bp}Polycyclic Aromatic Hydrocarbons (PAHs) are ubiquitous pollutants, that is: they are found in soil, air and water\textsuperscript{2,9}. They are named as such because they are composed of joined cyclic rings; thus, they tend to be of planar geometry. However, upon entering a biological system they are metabolised to more polar and multi-planar forms\textsuperscript{6}. This metabolisation is important to our understanding of the function PAHs because generally speaking, bio-important interactions do not occur without metabolisation. Additionally when biota have a method to metabolise a compound they tend to, our understanding of biota is that they favour lower entropy configurations and therefore utlize all compounds they can.\\
\hspace*{26 bp}It is thought that these metabolites of PAHs cause carcinogenesis by forming DNA-PAH complexes which then inhibit the proper use of DNA in cellular functions\textsuperscript{4,6,10}. We will explore evidence related to this hypothesis, and by doing so, examine the amounts of PAHs needed to form these adducts and thus predict possible ecological damage done by these pollutants. However, the purpose of this paper is to examine one PAH in particular, Benzo[b]fluoranthene (B[b]F), its metabolites, evidence of carcinogenesis, prevalence and possible ecological damages.
\section{Location and\\Distribution of PAHs}\]

Answer 6

yes you can.

Answer 7

and no, i didnt know there was a latex practice subsection

Answer 8

and yes, I know its actually just a PhP markup for /mathtools package

Answer 9

but I cant even get a section to show up properly atm

Answer 10

you can only close questions not delete them :P

Answer 11

PHP won't work here either i think

Answer 12

\(Introduction
Polycyclic Aromatic Hydrocarbons (PAHs) are ubiquitous pollutants, that is: they are found in soil, air and water\textsuperscript{2,9}. They are named as such because they are composed of joined cyclic rings; thus, they tend to be of planar geometry. However, upon entering a biological system they are metabolised to more polar and multi-planar forms\textsuperscript{6}. This metabolisation is important to our understanding of the function PAHs because generally speaking, bio-important interactions do not occur without metabolisation. Additionally when biota have a method to metabolise a compound they tend to, our understanding of biota is that they favour lower entropy configurations and therefore utlize all compounds they can.\\
It is thought that these metabolites of PAHs cause carcinogenesis by forming DNA-PAH complexes which then inhibit the proper use of DNA in cellular functions\textsuperscript{4,6,10}. We will explore evidence related to this hypothesis, and by doing so, examine the amounts of PAHs needed to form these adducts and thus predict possible ecological damage done by these pollutants. However, the purpose of this paper is to examine one PAH in particular, Benzo[b]fluoranthene (B[b]F), its metabolites, evidence of carcinogenesis, prevalence and possible ecological damages.\)

Answer 13

math processing error?

Answer 14

lol it really doesnt like trying to put a paper in this.

Answer 15

What I was trying to post, lol

Answer 16

maybe there's some problems with the mathjax scripts at the moment.

Answer 17

with the .tex

Answer 18

The version of latex this site uses is very limiting by the way :P you can't import any packages

Answer 19

yes, I know. lol

Answer 20

it seems to mostly be mathtools

Answer 21

yea and some fonts, color stuff, symbol packages

Answer 22

lol apparently you cant delete posts anymore

Answer 23

\[\usepackage[scaled]{helvet}
\renewcommand*\familydefault{\sfdefault}
\usepackage[T1]{fontenc test\]

Answer 24

never knew what was once possible xD

Answer 25

\[\usepackage[scaled]{helvet} Test \]

Answer 26

bleh, yeh , it used to be okay to delete questions
or maybe that was when i was a mod, idk, lol

Answer 27

I can't use my favourite font :(

Answer 28

nooo me neither i want kononar but it's not in the font list

Answer 29

where is this font list?

Answer 30

probably some are listed in the latex section (like \tt \mathbb \frak)