Daniel Machemer Dioxin toxicity: the state of scientific and environmental knowledge Dioxins and furans are a

family of compounds within the halogenated aromatic hydrocarbons (HAHs) that are closely related in their
chemical structures and mechanisms of toxicity. The term HAH describes their chemical structure. They are
hydrocarbons because they are primarily composed of hydrogen and carbon atoms. They are aromatic not by the
colloquial definition (i.e. these compounds do not have a distinct odor or aroma), but by the chemistry definition:
they contain benzene rings in their chemical structure. The term “halogenated” indicates that halogen atoms (in this
case, chlorine) are substituted at various positions on the benzene rings. Structurally, these compounds are planar
(flat), with two benzene rings connected by either one bridging oxygen molecule (furans) or two briding oxygen
molecules (dioxins). The benzene rings contain different numbers of chlorine atoms: General dioxin structure
General furan structure 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) Shown above are the general
structures for dioxins and furans, as well as the structure for 2,3,7,8-TCDD, the most toxic and most studied
compound in this family. There are 8 possible positions on the benzene rings at which chlorine atoms can be
substituted. Research has indicated that the substitution pattern of the chlorine atoms is related to their toxicity.
Scientists have devised two similar schemes to rank the toxicity of dioxins and furans, known as the International
Toxic Equivalency Factor (I-TEF) and the World Health Organization Toxic Equivalency Factor (WHO-TEF).
Under both schemes, 2,3,7,8-TCDD is assigned a TEF of 1, and all other congeners are O O O O O Cl Cl Cl Cl

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assigned a number less than 1 as a multiplier, based on their toxicity relative to 2,3,7,8- TCDD. The two schemes
differ only in their weighting of the toxicity of certain congeners. Dioxins and furans are environmental
contaminants that are commonly produced by combustion of fossil fuels, incineration of municipal waste, and as a
byproduct of pulp and paper bleaching and production of other chemicals. 2,3,7,8-TCDD, the most toxic member of
this family, is an endocrine disrupter as well as a potent animal carcinogen and teratogen which persists both in the
environment (due to its chemical stability) and in biological tissues (due to its resistance to metabolism). In 1997,
the International Agency for Research on Cancer classified 2,3,7,8-TCDD as a known human carcinogen. 2,3,7,8-
TCDD is known to cause immunosuppression, skin lesions known as chloracne, and a variety of other human health
problems after exposure to even low concentrations. Dioxins and furans are hydrophobic, and thus readily cross cell
membranes and affect subcellular systems in a variety of ways, many of which are not fully understood. Because
dioxins and furans persist in biological tissues, they are present in increasing concentrations in a given organism as
one moves up the food chain. Thus, the EPA has classified seven different dioxins and ten different furans as
persistent, bioaccumulative, and toxic, and these compounds are among the 12 groups of Priority PBTs because of
their effects on human health. The EPA gives an excellent summary of the risks of dioxins and furans on the PBT
web site, which can be found at [Link] Scientists have learned a great deal in
the past 15 years on the toxicity of certain dioxins and furans from laboratory experiments. However, there has been
some

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difficulty in applying what has been learned in the laboratory about dioxins and furans to solving the dioxin and
furan problem in the environment. Some of the problem is rooted in technology. Laboratory science has established
that dioxins and furans have subtle effects on biological systems at very low concentrations. These concentrations
were often below the threshold of detection of existing measurement technologies, until the early 1990s when
improved technologies became available. However, congener- specific detection is still problematic. This makes it
difficult to adequately assess the risks associated with specific environmental releases, since emissions are almost
always composed of a mix of congeners, with TEFs of the congeners differing by as much as a factor of 10000.
Dioxins and furans are covered under the EPA’s Toxics Release Inventory (TRI); thus, firms covered by this
program are required to report their releases of dioxins and furans. The map indicates the 37 sites in the state of
California that have reported measurable releases of dioxins and furans under the TRI. However, there is not
congener-specific data available for each release site, which makes risk assessment more difficult. Additionally,
these regulations only cover large, point source emissions. A variety of mobile and nonpoint source emissions are
not covered under existing regulatory requirements because it would be impractical to measure the dioxins and
furans contributed by these sources (for example, residential combustion of wood or trash, or automobile emissions).
The individual impact of a given source of this type may be small, but the collective environmental impact is larger.
Regulations have traditionally focused on measuring emissions at the source rather than environmental sampling to
determine the total dioxin and furan load in the air and the water. The lack

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of sampling data has meant that the impact of nonpoint sources of dioxins and furans on human health is not
adequately addressed or understood. The State of California has recognized this deficiency in the data, and has
recently embarked on several programs to monitor dioxin concentrations in the environment. However, these
programs only cover ambient concentrations in the air; water concentrations are not addressed. Testing of mobile
sources is under consideration, but has not yet begun. Sampling is also taking place only at select locations in the
San Francisco Bay area and the Los Angeles basin. These efforts will certainly yield useful additional data. But it
will be a number of years before this data becomes available, and the data will still be incomplete because it covers
only select regions.

Chemical structure of Sildenafil (Viagra).

PURPOSE: We assess the clinical efficacy of sildenafil citrate and predictors of

satisfactory outcome. MATERIALS AND METHODS: All patients treated with
sildenafil citrate within the first 6 weeks of its release were evaluated with a self-
administered questionnaire before and at completion of therapy to assess etiology of
erectile dysfunction, level of sexual function, libido, response to previous therapies,
response to therapy with sildenafil citrate and quality of life. Sexual function was
measured before and during therapy using an abbreviated version of the International
Index of Erectile Function, with a successful outcome defined as a level of satisfaction of
4 or 5 on a 5-point scale. RESULTS: Followup was obtained in 267 of the 308 patients
who entered the study. Mean age plus or minus standard deviation was 61+/-9.6 years
and duration of erectile dysfunction was 4.1+/-3 years. Overall satisfaction with sildenafil
citrate for the entire patient population was 65% and response to prior therapies did not
affect satisfaction. There was a significant positive correlation between baseline sexual
function and response to sildenafil citrate but even patients with severe erectile
dysfunction had a 41% satisfaction rate. Etiology of erectile dysfunction had a significant
impact on satisfaction rate, with neurogenic causes of erectile dysfunction (diabetes,
prostate surgery and so forth) having significantly lower rates than psychogenic or
vasculogenic erectile dysfunction. CONCLUSIONS: Sildenafil citrate is a highly
effective oral agent for the treatment of erectile dysfunction in clinical practice. The best
predictors for response to sildenafil citrate therapy are baseline sexual function and
etiology of erectile dysfunction. However, we could not identify any patient characteristic
that would predict absolute failure for sildenafil citrate therapy. Therefore, all patients
with erectile dysfunction who do not have specific contraindications should be
considered for sildenafil citrate therapy.

The molecular mechanisms of the effects of sildenafil, a specific inhibitor of cyclic

guanosine monophosphate (cGMP) phosphodiesterases are briefly reviewed. The second
messenger cGMP as well as its molecular targets (with the exception of the photoreceptor
signal transduction machinery) have long played an underdog role compared with cyclic
adenosine monophosphate and other signalling molecules such as inositoltrisphosphate.
The same holds for guanylyl cyclase, which, albeit being the main effector molecule of
the gaseous neurotransmitters carbon monoxide and nitric oxide (NO), has received much
 less attention relative to its activators and their synthases. Stimulation of the arginine -->
NO --> cGMP pathway by bypassing NO-synthase is a well-established pharmacological
principle in the treatment of cardiovascular disorders. In contrast, local application of
NO-donors or oral feeding of excessive amounts of precursor amino acid L-arginine to
treat erectile dysfunction were met with variable success or failure. The advent of a new
principle, amplification of the NO-signaling cascade by means of target organ selective
phosphodiesterase inhibition, has renewed interest in phosphodiesterases and cGMP.

Dioksin

Dioxin Overview
Dioxin is a shorthand name given to a family of 75 different chemical compounds with a similar chemical structure
and set of biological effects, though their potency varies widely. Dioxins are organochlorines, or compounds formed
when a chlorine molecule binds with a carbon molecule during combustion or in some type of industrial production
process. Dioxins cause cancer in humans and animals. Animal tests also show interference with reproduction,
development, and immune system function at low doses, raising substantial concern about current human exposure
levels.
The toxicity of a dioxin compound will vary depending on the number, and position within the molecule, of the
chlorine atoms. One of the most well known (and most toxic) forms of dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin,
or TCDD28. A colorless solid with no known odor, TCDD represents the standard when discussing the toxicity of a
dioxin or dioxin-like compound — other compounds are rated on their toxic equivalency factor (TEF) relative to
TCDD.
Dioxin is never intentionally produced, but it is nonetheless found all over the planet, primarily as a result of
incineration of municipal and medical wastes. Using sediment samples from lakebeds, scientists have found that
levels of dioxin in the environment increased significantly beginning around 1935-1940. According to the U.S.
Environmental Protection Agency's Science Advisory Board, the most likely explanation for this observation is the
combustion of chlorinated products in the waste stream during that period and thereafter. 29
Like many organochlorines, dioxin persists in the environment for long time periods. Minute quantities are found in
the soil and on the leaves of plants, which once ingested by grazing animals or fish, accumulates in their fat tissues.
As you move up the food chain, the concentration of dioxin stored in animal fat tissues greatly increases. Inuit
natives of Arctic Canada, for instance, although geographically far removed from any industrial processes, have
been shown to have elevated levels of dioxin, furans, and PCBs in their system, thanks to a diet dependent on fish
and other marine mammals.30

Health Effects of Dioxin

Along with many other scientific, university, and industry researchers, the U.S. Environmental Protection Agency
has been investigating the causes and impacts of dioxin generation for many years. In 1983, 1988, and 1994, the
EPA prepared assessments of the human health risks from exposure to dioxin. In the latest report, EPA concluded
that the "weight of the evidence evaluation suggests that dioxin and related compounds...are likely to present a
cancer hazard to humans."31 The report also concluded that an increased risk of diabetes and altered reproductive
hormone levels appear to be long term consequences of exposure to TCDD.32
Some of the specific studies highlighted in the EPA report and in other scientific journals which have looked at
specific health impacts of low doses of dioxin on humans and other animals include the following:
 Tests involving monkeys show an association between dioxin exposure and endometriosis, which is an
abnormal growth of the uterine lining outside of the uterine cavity.33
 In human infants, dioxin lowers thyroid hormone levels, hormones which are necessary for normal brain
development.34
 In laboratory animal experiments, dioxin exposure has caused decreased immune response and increased
susceptibility to infections.35,36,37
 A number of studies have identified dioxin as an endocrine (or hormone) "disrupter," causing both male
and female reproductive disorders. Laboratory animals exposed to low doses of dioxin have produced
offspring with lowered testosterone levels, decreased sperm counts, and birth defects. 38 Dioxin exposure
among female laboratory animals has also resulted in decreased fertility, decreased litter size, and inability
to carry pregnancies to term.39,40
Dioxin's role as an endocrine disrupter is perhaps the most critical threat, as it may be fostering long term changes in
human reproductive capabilities of which we are not yet aware. The roughly 75 years that industrial chlorine use has
become prevalent may be too short a time frame to see significant, observable changes in human reproductive
patterns. However, some researchers believe that endocrinal changes noted in other species with shorter generational
timeframes are reason enough to pursue changes that would lessen or eliminate the continued loading of dioxin into
our environment.41
In May 1997, the U.S. Environmental Protection Agency published a notice in the Federal Register proposing to add
dioxin to the Toxic Release Inventory (TRI). The TRI is a list of chemicals and chemical categories subject to
federal reporting requirements when manufactured or used in large quantities. Chemicals and compounds on the list
are considered to be toxic, and the list is made public to allow citizens to learn about the sources and quantities of
hazardous substances released to the environment in or near their communities.

Sources of Dioxin
In June 1994, the U.S. EPA released a report analyzing exposure to dioxin-like compounds.42 The report was
released in draft form, and still has not been finalized by the EPA. Nonetheless, the report has been widely cited as
the most authoritative source of information on dioxin exposure.
In that report, four major types of sources of dioxin were identified:
 Industrial processes, such as chlorine bleaching of wood pulp for paper making.
 Chemical manufacturing sources, such as the production of chlorinated compounds.
 Combustion/incineration sources, such as hazardous waste, medical waste, or municipal solid waste
incinerators.
 Reservoir sources, such as particles of dioxin that had previously settled into sediment but were disturbed
during dredging operations.
Within these categories, the EPA cited municipal solid waste (MSW) and medical waste incinerators as the most
significant sources of dioxin in the environment, collectively accounting for roughly 85-87% of all known annual
dioxin emissions.43 Cement kilns (which often burn hazardous waste as a fuel source), secondary copper smelters
(which often smelt plastic coated copper wire), diesel engines, and industrial wood burning operations were cited as
other important sources of dioxin emissions.

1. What are dioxins ?

1.1. "Dioxins" refers to a group of chemical compounds that share certain chemical structures and biochemical
features: polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Certain
polychlorinated biphenyls (PCBs) show a strong resemblance to dioxins. Dioxins have no use, they are byproducts
of human activities and natural processes. They are relatively stable, highly soluble in lipids, slowly metabolized and
therefore tend to accumulate in food chains. Dioxins with closely related chemical structures are referred to as
"congeners".
1.2. Dioxins are formed by combustion processes. Most of the dioxins are/were produced upon combustion of PCBs
or chlorine containing products. Dioxins can be formed by non-selective household trash burning, natural processes
such as forest fires, chlorine bleaching of pulp and paper and other industrial processes.
1.3. Historically, non-selective commercial and municipal waste incineration, manufacture and use of dioxin
containing herbicides and chlorine bleaching resulted in major releases of dioxins to air and water. Regulatory and
voluntary industry actions and the development of efficient filtering and destruction systems have resulted in a
substantial reduction of emissions. Uncontrolled burning of non selected residential waste is now thought to be
among the major sources of dioxins.
2. How is the population exposed to dioxins ?
2.1. Over 90 percent of human dioxin and PCB intake is through food from animal origin. Dioxins contribute to
about 1/3 of it, dioxin-like PCBs to the other 2/3rd. Diets low in animal fat lead to a lower dioxine intakes. The total
body burden of dioxins and PCBs steadily increases, stabilizing about the age of 20. In most western countries,
dioxin and PCB levels decreased by almost a factor of 2 during the last decade. More...
2.2. Accidental exposure to PCDDs, PCDFs and PCBs occurred in Seveso Italy. Incidents involving contaminated
food oil at Yusho Japan and YuCheng Taiwan led to dioxin food exposure 100,000 higher than normal levels. Other
cases report occupational exposure of workers in pesticide producing plants and related industries. More...
2.3. Dioxin-like compounds mediate their biological effects by interacting with a cellular dioxin receptor, leading to
cancer, neurodevelopmetal, cardiovascular effects and in some cases, diabates. Mechanism of dioxin toxicity are
similar in man and other vertebrates. More...

Porphyrin

Porphyrins (pronounce) are tetrapyrroles. They consist of four weakly aromatic pyrrole
(pronounce) rings joined by methene bridges.

Tetrapyrroles are major constituents of every living cell. They play important roles in electron transport
systems and function as prosthetic groups of many enzymes. Due to their importance to all living systems
and their intense coloring, they have been nicknamed the "pigments of life". Cyclic tetrapyrrole derivatives
are derived from a common porphorinogen structure in which the four pyrrolic rings are usually linked by
methine bridges. All four rings are at various oxidation levels and, depending on the tetrapyrrole class,
have various substituents. Metal ions such as iron, magnesium, cobalt and nickel can be complexed by
the central nitrogen atoms. Because porphyrins are among the best ligands known in terms of
thermodynamic stability and kinetic non-lability and because they display unique physical, chemical and
biological properties not found in simple acyclic or non-aromatic compounds, they are one of the most
widely studied class of all macrocyclic systems.
Porphyrins have long been of interest for biomedical applications. Drugs based on porphyrins have been
or are currently developed for e.g. photodynamic treatment of cancer, treatment of psoriasis and viruses,
gene regulation therapies and more recently, drug targeting. Other innovative porphyrin applications are
in material science and chemistry. Expanded porphyrins with increased numbers of -electrons, which
absorb light at wavelength greater than 630 nm, are of particular interest for biomedical laser applications
such as photodynamic treatment of cancer. Metalloporphyrins find applications e.g. in electro-catalysis, as
electrodes in fuel cells or as chemical sensors.
Porphyrins can be chemically synthesized by either total synthesis or functional derivatisation of haem or
chlorophyll derivatives. However, many regio- and stereoselective functionalizations of porphyrins cannot
be achieved chemically. Furthermore, chemical synthesis of porphyrin derivatives usually requires several
steps resulting in low overall yields, which makes porphyrins very expensive compounds. In particular,
chemical synthesis of expanded porphyrins remains a challenge in regards of obtaining significant yields
and configurational isomer purity. A biocatalytic approach using regio- and stereoselective enzyme
catalysts, on the other hand, could produce novel porphyrin structures in good yields.
Presently, studies on natural porphyrins have been focused on elucidating the biochemistry and genetics
of porphyrin biosynthesis in cells, rather than on engineering recombinant cells for the production of
porphyrins. The commercial production of vitamin B12 by engineered Pseudomonas and Propionibacteria
demonstrates most impressively the capabilities of microorganisms to produce porphyrins in large
quantities. Although porphyrin biosynthesis is one of the most extensively studied metabolic pathways,
still not all biosynthetic enzymes have been cloned, the catalytic functions of a number of enzymes
remain to be investigated and structural information is available only for a small number of biosynthetic
enzymes. Presently, co-enzyme B12 biosynthesis is the most complex biosynthetic pathway ever
elucidated, where up to 30 genes are involved. Haem biosynthesis is the most extensively studied
porphyrin pathway for which a number of biosynthetic genes are available (Figure 1).
We are evolving in vitro novel pathways that allow us to biosynthetically produce new unnatural porphyrin
structures with various reactive functional groups which will make them valuable scaffolds for chemical
modifications for the synthesis of additional porphyrin structures. To do this, we had first to engineer E.
coli cells to produce large quantities of porphyrins - presently, no efforts have been undertaken to
engineer E. coli cells specifically for porphyrin overproduction, although bacteria have the capabilities to
overproduce porphyrins. Figure 2 shows engineered E. coli cells that overproduce porphyrins.

· What is “Normal-Coordinate Structural Decomposition”

The possible biological significance of nonplanar porphyrin structures in proteins has been suggested by several
research groups. For example, a moderate nonplanar distortion of the heme is observed in the crystal structures of
the mitochondrial cytochromes c, and this characteristic distortion is generally conserved in proteins isolated from
different species. The importance of these nonplanar heme structures is underscored by the observation that the
heme is nonplanar only if the surrounding protein exerts the necessary external forces on the prosthetic group. In
contrast, the isolated heme group in solution is planar. Thus it is reasonable to suggest that nonplanar porphyrins and
protein-induced changes in the nonplanarity may provide a mechanism for protein modulation of biological
properties. Because of the complexity of the distortions of porphyrin molecules, it becomes necessary to have a
simple, precise, and universal method to describe their deformations.
The Normal-Coordinate Structural Decomposition (NSD) method describes the nonplanar porphyrin structures in
terms of the equivalent displacements along the lowest-frequency normal coordinates of the porphyrin macrocycle.
The description of a porphyrin structure in terms of the normal coordinates is a uniquely useful way of
characterizing the macrocyclic structure. Unlike other descriptions, the normal coordinate structural decomposition
method occupies a special status because of the unique relationship between the macrocyclic distortion energies and
the displacements along the normal coordinates of vibration. In other words, if the displacement for each normal-
coordinate deformation is known, then the total macrocyclic-distortion energy can be readily estimated as a sum of
energies for each mode, assuming that the vibrational frequencies are known. Perhaps more importantly, a great
simplification occurs when the porphyrin distortion is expressed in terms of normal coordinates. The simplification
results from the fact that only a few displacements (six out-of-plane and six in-plane) along the lowest frequency
modes of the macrocycle must be specified to adequately characterize the distortion.

The significance and diversity of the biological functions of porphyrin molecules in nature have always been
appreciated in photosynthesis and respiration:
Co2 + H2O --chlorophylls--- C(H2O) + O2
---hemoproteins---

Among hemoproteins the role of the heme group spans a broad spectrum of functions ranging from oxygen transport
(hemoglobin) to electron transport (cytochrome c) to drug detoxification (cytochrome P-450). To understand the
underlying principles that govern the reactivities and functions of the heme prosthetic group has always been the
goal of our research. Most heme catalysts involve either a valence change at the metal center or an altering of the
redox state of the porphyrin ring or both. It is the unusual flexibility of the porphyrin system to accommodate
extreme redox changes, coupled with the convenient coordination and electron-transfer ability of the metal center
that makes the metalloporphyrins such versatile catalysts.
Variations in heme functions can be brought about by axial ligand, steric and environmental effects. These effects
can often be tested and amplified individually by using suitable synthetic model compounds. Since porphyrin
syntheses can be lengthy and difficult, we are developing better ways to synthesize these heterocyclic molecules.
The investigation of the properties of model systems also necessitates the use of a wide variety of modern
instrumentation and experimental techniques including UV-VIS, NMR, EPR and resonance Raman spectroscopy,
CV and other electrochemical analyses, stopped-flow and flash photolysis.
Some examples of bacterial heme prosthetic groups characterized and synthesized in our laboratory include those
diagrammed here.

Genome

From June 13 - June 23, 1996, the 2nd EL.B.A. Foundation course on Genome, a NATO Advanced Study Institute,
was held at Marcian Marina, Isle of Elba, co-sponsored by the North Atlantic Treaty Organization and the EL.B.A.
Foundation. The subject of the course was "Genome Structure and Function" with participants selected from 15
different countries. The purpose of the course and of the resulting book (NATO ASI SERIES 3-31) is the study of
DNA structure (from the primary to the quinternary) and gene expression in the control of cell function and well
cycle progression. The topics were presented by experts and scientists active in the field, with the aim of giving an
insight into modern problems of genome study and recent achievements in related fields of molecular and cell
biology, genetic engineering and biophysics, oncology and biotechnology. This resulting book is intended to give a
broad perspective of the current status of these fields. The major emphasis is towards a deep understanding of DNA
structure anmd function in interphase and metaphase chromosomes, originating in the parallel biophysical (namely
NMR X-Ray and neutron scattering, spectropolarimetry, image analysis, calorimetry) and biochemical study
conducted on a wide range of cell systems placing the emphasis on either the higher order DNA structure or gene
structure and function. To exemplify the importance of genome studies for practical applications, the book also
addresses the industrial utilization of recombinant DNA in agriculture and health, and the novel or non-conventional
instrumentation for the study of DNA isolated or in situ (scanning probe microscopy, synchrotron radiation,
biosensors, LB trough, silicon chip). The topics cover multiple aspects of genome studies, ranging from gene
regulation, transcriptional control of cell cycle, domain organization of the genome, to large scale chromatin
structure, structual studies of chromatin up to tumorigenesis and plant gene technology.

HCV viral particles harbor a single plus-strand RNA that has a length of 9600 nucleotides (figure 2). It can be
translated as a mRNA within the host cell. A single open reading frame (ORF) is translated into a polyprotein whose
cleavage produces the individual structural and nonstructural proteins. Translation of the HCV ORF is directed via a
340 nucleotides long 5' non-translated region (NTR) functioning as an internal ribosome entry site (IRES). The 3'
NTR is essential for replication.

P35) Complete genome sequences have been determined in a variety of species such as pathogenic bacteria, yeast,
and human. Information obtained from these complete sequences gives us an opportunity to study evolutionary
change of the whole genome structure. We have so far shown that genome structures had been shuffled frequently
among eubacteria [1]. Moreover, we found that operon structures, which are generally thought to be important
functional units, were rather unstable in the course of long-term evolution [2]. Since we attempted to include
remotely related organisms such as eukaryotes in this study, we further improved our method for detecting
orthologous gene pairs in the following two points. First, we employed log-normalized Smith-Waterman scoring so
as to set a better threshold for sequence similarity significance. Second, we took into consideration gene duplication
and fusion events after speciation. Searching for conserved orthologous gene orders in complete genomes between
archaebacteria and eubacteria, we reconstructed their ancestral genome structure and then examined the changes of
genome structures after the divergence from the ancestor. As a result, we found that the degree of genome instability
was quite different among the species examined, and that this degree was correlated with the occurrence frequency
of insertion sequences (ISs), which are known to be interspersed repetitive sequences. Accordingly, IS appears to
strongly affect genome instability, probably because it mediates homologous recombination frequently. In fact, our
previous analysis indicates that ISs have been transposed with considerable frequency during short-term evolution
[3]. Next, we turned our attention to a eukaryotic genome structure. Eukaryotes have a unique genome structure in
that they may have lost prokaryotic operon structures, and possibly experienced a drastic change of transcription
regulation systems. However, it is unlikely that all prokaryotic operons were suddenly destroyed in the ancestor of
eukaryotes, but its gene regulations were completely retained. The eukaryotic genome structure must have formed
gradually in the course of evolution. Thus, we attempted to analyze gene fusion in the yeast genome, and found that
yeast possesses more fused genes than prokaryotes. Moreover, all of these fused genes seem to have been derived
from prokaryotic operon structures. This observation implies that a lot of gene fusion events preceded loss of operon
structures, and then completely monocistronic transcription regulation, which is generally observed in modern
eukaryotes, was established. Gradualism may explain a large gap between the genome structures of prokaryotes and
eukaryotes.

Arochlor
1. Arochlor is the common name for polychlorinated biphenyls (PCBs).
 Synopsis on dioxins and PCBs

General introduction
Burning produces dioxins
Dioxins and some PCBs cause multiple toxic effects.
Dioxins and PCBs accumulate in the human body.
Risk assessment is tricky.
Common sources of errors and practical difficulties.

Polychlorinated biphenyls (PCB-compounds) are a group of oily stable chemicals, which have been used because
of their stability and low flammability as insulating materials in electrical equipment (transformers and capacitors),
as plasticizers (softening materials) in plastic products, and for a variety of other industrial purposes. Their stability
is a technical advantage, but it also means that they are extremely persistent in the environment. They also
contain small amounts of dioxin impurities especially PCDFs, some of which are much more toxic than the main
chemicals.
The production and use of PCBs have been discontinued in most countries, but large amounts remain in electrical
equipment, plastic products, buildings (e.g. plastic carpeting, sealing materials), and in the environment. Because
PCBs are considered problem waste, their disposal is expensive, and may sometimes lead to attempts to dispose of
them by mixing them to other waste products. Two well-established environmental accidents have occurred, called
Yusho (Japan) and Yu-Cheng (Taiwan). In both cases rice oil was contaminated and caused a number of health
effects.
Polychlorinated dibenzo-p-dioxins (PCDDs) and related halogenated aromatic hydrocarbons (e.g., PCDFs), often
called "dioxins" as a group, are ubiquitously present environmental contaminants. Some of them, notably TCDD
(2,3,7,8-tetrachlorodibenzo-p-dioxin) belong to the most toxic synthetic compounds known. They are very stable
against chemical and microbiological degradation and therefore persistent in the environment. They are fat-soluble
and thus tend to bioaccumulate in tissue lipid and in the food chain. These factors increase their potential hazards to
humans and animals.

What are PCBs?

PCBs : Polychlorinated biphenyls. A class of organics produced by chlorination of a biphenyl.

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What are the uses of PCBs?

PCBs were very popular in commercial & industrial circles. The uses for them were many and varied, but some
examples of products they were used include :
 Electrical & heat conduction
 Flame retardants
 plastics
 rubber
 paints & dyes
 transformers (electricity)
What are the dangers of PCBs?

PCBs have been found to be both toxic and carcinogenic. That means that they have damaging affects on both
organisms (including humans) and where they exist.
 Environmental Effects
 Contamination : PCBs have been found in the atmosphere, soil, water, sediment, fish & wildlife.
 Bioaccumulation : concentrations of these persistant chemicals are stored in organisms so their
concentration increases greatly with every step in a food chain. Each upward level therefore has
compounded problems.
 Health Effects
  PCBs have been proven to cause cancer in animals. They are also probable causes of cancer
within humans.
 PCBs have been found to damage the immune system, the reproductive system, the neurological
system & the endocrine system in both animals and humans.
 Changes in the levels of PCBs within the blood system has been found to cause liver problems
(due to filtration damage) & problems with the blood chemical levels themselves.
The amount of negative effects PCBs were having quickly came to outweigh the advantages of their uses.
Examples of PCB contaminations : The DEW Lines

Along with general information, this site contains information on a more specific example : The DEW Lines. These
were part of the cold war warning system placed in Canada by the American government. When considering
biomagnification, their presence and lack of further care allowed PCBs to contaminate the land around them. When
considering legislation, these are even more of an issue due to the debate of which government should have the
responsibility of caring for this contamination.