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Genotoxicity

From Wikipedia, the free encyclopedia

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Genotoxicity describes a deleterious action on a cell's genetic material affecting its integrity. Genotoxicsubstances are known to be potentially mutagenic or  carcinogenic, specifically those capable of causing

genetic mutation and of contributing to the development of  tumors. This includes both certain chemicalcompounds and certain types of radiation.

Typical genotoxins like aromatic amines are believed to cause mutations because they are nucleophilic and

form strong covalent bonds with DNA resulting with the formation of Aromatic Amine-DNA Adducts, 

 preventing accurate replication.

Genotoxins affecting sperm and eggs can pass genetic changes down to descendants who have never been

exposed to the genotoxin.

Toxicology

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sToxicology (from the Greek  words τοξικός - toxicos "poisonous" and logos) is a branchof biology and medicine concerned with the study of the adverse effects of  chemicals on

living organisms.[1] It is the study of symptoms, mechanisms, treatments and detection of 

 poisoning, especially the poisoning of people.

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 [ edit  ] History 

LgSsHssDioscorides, a Greek physician in the court of the Roman emperor Nero, made the first

attempt to classify plants according to their toxic and therapeutic effect.[2] Ibn Wahshiya

wrote the Book on Poisons in the 9th or 10th century.[3]

Mathieu Orfila is considered to be the modern father of toxicology, having given thesubject its first formal treatment in 1813 in his Traité des poisons, also called Toxicologie

 générale.[4]

In 1850 Jean Stas gave the evidence that the Belgian Count Hypolyte Visart de Bocarmé

killed his brother-in-law by poisoning with nicotine[5] 

Theophrastus Phillipus Auroleus Bombastus von Hohenheim (1493–1541) (also referred

to as Paracelsus, from his belief that his studies were above or beyond the work of  Celsus 

- a Roman physician from the first century) is also considered "the father" of toxicology.[6]

He is credited with the classic toxicology maxim, " Alle Dinge sind Gift und nichts ist ohne Gift; allein die Dosis macht, dass ein Ding kein Gift ist." which translates as, "All

things are poison and nothing is without poison; only the dose makes a thing not a

 poison." This is often condensed to: "The dose makes the poison".

The relationship between dose and its effects on the exposed organism is of highsignificance in toxicology. The chief criterion regarding the toxicity of a chemical is the

dose, i.e. the amount of exposure to the substance. All substances are toxic under the

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right conditions. The term LD50 refers to the dose of a toxic substance that kills 50

 percent of a test population (typically rats or other surrogates when the test concerns

human toxicity). LD50 estimations in animals are no longer required for regulatorysubmissions as a part of  pre-clinical development  package.[citation needed ]

The conventional relationship (more exposure equals higher risk) has been challenged inthe study of endocrine disruptors.

 [ edit  ] Toxicity of metabolites

Many substances regarded as poisons are toxic only indirectly. An example is "woodalcohol," or methanol, which is chemically converted to formaldehyde and formic acid in

the liver . It is the formaldehyde and formic acid that cause the toxic effects of methanol

exposure. As for drugs, many small molecules are made toxic in the liver, a goodexample being acetaminophen (paracetamol), especially in the presence of chronic

alcohol use. The genetic variability of certain liver  enzymes makes the toxicity of many

compounds differ between one individual and the next. Because demands placed on oneliver enzyme can induce activity in another, many molecules become toxic only in

combination with others. A family of activities that many toxicologists engage includes

identifying which liver enzymes convert a molecule into a poison, what are the toxic

 products of the conversion and under what conditions and in which individuals thisconversion takes place.

 [ edit  ] Subdisciplines of toxicology 

There are various specialized subdisciplines within the field of toxicology that concern

diverse chemical and biological aspects of this area. For example, toxicogenomics 

involves applying molecular profiling approaches to the study of toxicology.[7]

Other areas include Aquatic toxicology, Chemical toxicology, Ecotoxicology, Environmental

toxicology, Forensic toxicology, and Medical toxicology.

 [ edit  ] Chemical toxicology 

Chemical toxicology is a scientific discipline involving the study of structure and

mechanism related to the toxic effects of chemical agents, and encompasses technology 

advances in research related to chemical aspects of toxicology. Research in this area isstrongly multidisciplinary, spanning computational chemistry and synthetic chemistry,

 proteomics and metabolomics, drug discovery, drug metabolism and mechanisms of 

action, bioinformatics, bioanalytical chemistry, chemical biology, and molecular epidemiology.

Toxicity

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sbxToxicity is the degree to which a substance can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal,  bacterium, or   plant, as well as the

effect on a substructure of the organism, such as a cell (cytotoxicity) or an organ

(organotoxicity), such as the liver (hepatotoxicity). By extension, the word may be

metaphorically used to describe toxic effects on larger and more complex groups, such asthe family unit or society at large.

A central concept of  toxicology is that effects are dose-dependent; even water can lead towater intoxication when taken in large enough doses, whereas for even a very toxicsubstance such as snake venom there is a dose below which there is no detectable toxic

effect.

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 [ edit  ] Types of toxicity 

There are generally three types of toxic entities; chemical, biological, and physical:

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 [ edit  ] Measuring Toxicity 

Toxicity can be measured by its effects on the target (organism, organ, tissue or cell).Because individuals typically have different levels of response to the same dose of a

toxin, a population-level measure of toxicity is often used which relates the probabilities

of an outcome for a given individual in a population. One such measure is the LD50.

When such data does not exist, estimates are made by comparison to known similar toxicthings, or to similar exposures in similar organisms. Then "safety factors" are added to

account for uncertainties in data and evaluation processes. For example, if a dose of toxinis safe for a laboratory rat, one might assume that one tenth that dose would be safe for a

human, allowing a safety factor of 10 to allow for interspecies differences between two

mammals; if the data are from fish, one might use a factor of 100 to account for the

greater difference between two chordate classes (fish and mammals). Similarly, an extra protection factor may be used for individuals believed to be more susceptible to toxic

effects such as in pregnancy or with certain diseases. Or, a newly synthesized and

 previously unstudied chemical that is believed to be very similar in effect to another compound could be assigned an additional protection factor of 10 to account for possible

differences in effects that are probably much smaller. Obviously, this approach is veryapproximate; but such protection factors are deliberately very conservative and themethod has been found to be useful in a deep variety of applications.

Assessing all aspects of the toxicity of cancer-causing agents involves additional issues,

since it is not certain if there is a minimal effective dose for carcinogens, or whether the

risk is just too small to see. In addition, it is possible that a single cell transformed into acancer cell is all it takes to develop the full effect (the "one hit" theory).

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It is more difficult to the toxicity of chemical mixtures than of single, pure chemicals

 because each component display its own toxicity and components may interact to

 produce enhanced or diminished effects. Common mixtures include gasoline, cigarettesmoke, and industrial waste. Even more complex are situations with more than one type

of toxic entity, such as the discharge from a malfunctioning sewage treatment plant, with

 both chemical and biological agents.

Environmental toxicology

vgsEnvironmental Toxicology (EnTox)

EnTox is a young (1965) and interdisciplinary science that uses both basic and appliedscientific knowledge to understand natural and anthropogenic pollutants life cycle and

their impacts upon structure and functions of biological and ecological systems. Research

in EnTox includes both laboratory experiments and field studies. EnTox wants to answer two main questions [1] (1) How the release pollutant causes harmful effects? (2) What can

we do to prevent or minimize risk to biological and ecological system?

EnTox objective is breakdown into a 5-steps understanding process useful for research/regulation[2]:

• Release of pollutant into the environment

• Transport and fate into biota (with/out chemical transformation)

• Exposure to biological and ecological system

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• Understanding responses and/or effects (molecular to ecological systems)

• Design experiments, remediation, minimization, conservation, and risk assessment

 plans tounderstand, eliminate, prevent or predict environmental and human health pollutions

situations.

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 [ ed it  ] The EnTox confusion

People misunderstand EnTox as a scientific discipline that only focus on chemicals into the environment.

 Not true. That represents environmental chemistry and chemodynamics. Environmental toxicology covers

more than only chemicals into the environment; it also includes studying and understanding the adverse

effects caused by those chemicals' release into the environment on living systems such as wildlife, aquaticspecies, pets, humans and ecological systems. Furthermore, the rich fabric of ideas, core concepts, literature

 body, technology and ideologies that merge together to develop EnTox is rather a dissimilar processthrough most educational institutions[3]. This may be the point in case that EnTox is a young

interdisciplinary science and controversy regarding what to include in a curriculum is an on going matter of 

discussion[4].

 [ edit  ] H ow to identify the blur lines interconnecting basic concepts

Reading the objectives for each discipline that merge into EnTox should decrease the confusion:

• Classical toxicology protects human (subcellular to individual) from toxic substances at concentration thatare harmful.

• Ecotoxicology (ecology + toxicology) want to protect many individuals, populations, communities and

ecosystems from exposure to toxic substance at concentration that are harmful.

• Environmental science is an interdisciplinary science that studies the earth, air, water, living environments

and social components.

• Environmental chemistry and chemodynamics is the study of chemical sources, reactions, transports,

effects and fate in the environment.

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Therefore, although these terms do not mean the same, they are related through a linear logical progression

(Pollutant Release-Exposure-Dose-Response Paradigm). EnTox embraces both disciplines: classical

toxicology and ecotoxicology. Further, it includes other sciences (read below) to make a more logicalapproach to understanding and solving real and complex pollution problems that society faces today or will

encounter in the future. The interdisciplinary core of EnTox borrows heavily from a range of disciplines

such as: environmental science, environmental chemistry and chemodynamics, analytical chemistry,

organic chemistry, biochemistry, molecular genetics, cell biology, genomics, pharmacology, pharmaco-and toxico-kinetics, physiology, mathematics and statistics, computer modeling, risk assessment, soil

science, geology, ecology, meteorology, marine biology and oceanography, limnology, and wildlife

 biology [5].

 [ edit  ] What is an environmental toxicologist and where they get jobs/careers?

An environmental toxicologist is a scientist who possesses an interdisciplinary training and uses a variety

of disciplines, skills and tools to determine the source, fate, transformation, effects, and risks of pollutantson the environment, wildlife, human health and ecosystems[6].

EnTox get hired by: 1. Academia 2. Government 3. Pharmaceutics/chemicals industries 4. Consulting

services 5. Others (non-profits, consumer products, etc). The Society of Toxicology have good information

about where toxicologist get jobs (Resource Guide to Career in Toxicology).

Xenobiotic

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From Wikipedia, the free encyclopedia

Jump to: navigation, search 

 Not to be confused with xenobiology.

A xenobiotic is a chemical which is found in an organism  but which is not normally produced or expected

to be present in it. It can also cover substances which are present in much higher  concentrations than are

usual. Specifically, drugs such as antibiotics are xenobiotics in humans because the human body does not produce them itself, nor are they part of a normal diet.

 Natural compounds can also become xenobiotics if they are taken up by another organism, such as the

uptake of natural human hormones by fish found downstream of sewage treatment plant outfalls, or the

chemical defenses produced by some organisms as protection against predators.

However, the term xenobiotics is very often used in the context of   pollutants such as dioxins and

 polychlorinated biphenyls and their effect on the biota, because xenobiotics are understood as substances

foreign to an entire biological system, i.e. artificial substances, which did not exist in nature before their 

synthesis by humans. The term xenobiotic is derived from the Greek words ξένος (xenos) = foreigner,

stranger and βίος (bios, vios) = life, plus the Greek suffix for adjectives -τικός, -ή, -ό (tic).

Contents

[hide]

• 1 Xenobiotic metabolism

• 2 Xenobiotics in the environment

• 3 Inter-species organ transplantation

• 4 See also

• 5 References

• 6 External links

 [ edit  ] Xenobiotic metabolism

Main article: Xenobiotic metabolism

The body removes xenobiotics by xenobiotic metabolism. This consists of the deactivation and the

secretion of xenobiotics, and happens mostly in the liver. Secretion routes are urine, faeces, breath, andsweat. Hepatic enzymes are responsible for the metabolism of xenobiotics by first activating them

(oxidation, reduction, hydrolysis and/or hydration of the xenobiotic), and then conjugating the activesecondary metabolite with glucuronic or sulphuric acid, or glutathione, followed by excretion in bile or 

urine. An example of a group of enzymes involved in xenobiotic metabolism is hepatic microsomal

cytochrome P450. These enzymes that metabolize xenobiotics are very important for the pharmaceutical

industry, because they are responsible for the breakdown of medications.

Organisms can also evolve to tolerate xenobiotics. An example is the co-evolution of the production of tetrodotoxin in the rough-skinned newt and the evolution of tetrodotoxin resistance in its predator, thecommon garter snake. In this predator-prey pair, an evolutionary arms race has produced high levels of 

toxin in the newt and correspondingly high levels of resistance in the snake.[1] This evolutionary response is

 based on the snake evolving modified forms of the ion channels that the toxin acts upon, so becoming

resistant to its effects.[2]

 [ edit  ] Xenobiotics in the environment 

Main article: Environmental xenobiotic

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Xenobiotic substances are becoming an increasingly large problem in Sewage Treatment systems, since

they are relatively new substances and are very difficult to categorize. Antibiotics, for example, were

derived from plants originally, and so mimic naturally occurring substances. This, along with the natural

monopoly nature of municipal Waste Water Treatment Plants makes it nearly impossible to remove this

new pollutant load.

Some xenobiotics are resistant to degradation. For example, they may be synthetic organochlorides such as plastics and pesticides, or naturally occurring organic chemicals such as polyaromatic hydrocarbons

(PAHs) and some fractions of crude oil and coal. However, it is believed that microorganisms are capable

of degrading almost all the different complex and resistant xenobiotics found on the earth.[3] Many

xenobiotics produce a variety of biological effects, which is used when they are characterized using

 bioassay.

 [ edit  ] Inter-species organ transplantation

Main article: Xenotransplantation

The term xenobiotic is also used to refer to organs transplanted from one species toanother. For example, some researchers hope that hearts and other organs could be

transplanted from pigs to humans. Many people die every year whose lives could have been saved if a critical organ had been available for transplant. Kidneys are currently themost commonly transplanted organ. Xenobiotic organs would need to be developed in

such a way that they would not be rejected by the immune system.

Health effects of xenobiotics

One possible translation of "xenobiotics" is "foreign to life". In other words, any

substance that has no useful function in the metabolism of a living organism is xenobiotic to it. Such substance can't do you no good but, boy, can it make a havocof your health! The bad news is that xenobiotics are everywhere: in the air you're

inhaling, the water you drink, the food you eat - in the cloths you wear, things youhold and touch - even implanted into your body!

And the more of them gets inside you, the more xenobiotic - or foreign to life - youbecome yourself.

Xenobiotics can be natural substances occurring in plants, other animals, or theenvironment. They also can be man-made. The sad part is that most of xenobiotic

contamination is produced by man: it is us doing it to ourselves.

Natural food toxins

Is there such thing as natural food toxins? You bet. Not all natural, whole foods areequally good, and some can be plain unhealthy. How can naturally occurring food

substances be harmful to the body? Well, we live in imperfect world, and our food ispart of it: some food substances are just capable of disrupting our metabolic cycle.

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There is an untold number of natural chemical compounds in our foods, and not all of them are friendly to us. The offending substances are either biologically active

amines - like tyramine, histamine and serotonin - or natural plant toxins, such areglycoalkaloids in nightshades (potatoes, tomatoes, peppers, eggplant, tobacco, some

spices), cyanogenic glucosides (bitter almond, cassava root, sorghum root, limabean, fruit seed, etc.) , or pyrrolizidine alkaloids in some herbs and herbal teas.

These natural food toxins are adversely affecting health of millions, most of themunaware of what is causing - or contributing to - their health problem. Symptoms

caused by natural food toxins include food sensitivities and allergies, neurologic,cardiovascular or respiratory disturbances, arthritis, and liver damage.

 

Man-made toxins

While natural food toxins are definitely a health concern, toxic chemicals of 

industrial and agricultural origin are simply overwhelming. What else to say but:beware! Volatile hydrocarbons, dioxins, toxic metals, pesticides, herbicides,

insecticides, fungicides, chemical fertilizers, food additives, chlorine and fluoride - tolist only some of the major ones - are everywhere.

There are tens of thousands of tons of PCBs (polychlorinated biphenyls) in the upper200m of the North Atlantic, after three decades (1947-1977, when they were

banned) of dumping them into the Hudson River. After another three decades, theEPA finally made the GE responsible for cleaning the worst spots of the contaminated

river sediments, which should take place in 2009-2016. The ocean, of course,remains contaminated. And that is just the tip of the iceberg.

Plasticizers (or phthalates), common in PVC materials, plastic food packaging andcosmetics, are another endocrine (hormone) and cellular disruptor. These chemical

substances are either inherently toxic to our bodies, or become toxic due to theirexcessive accumulation. They accumulate in our tissues, damage our enzymes,

mimic our hormones and deplete the body of nutrients it needs for detoxication,making it ever more vulnerable.

Chemical toxins are capable of disrupting body chemistry in many ways. Possibleconsequence is any imaginable symptom or disease.

The final nail to the coffin of our health, suffering from all kinds of diseases due totoxic chemical exposures, as well as poor dietary and lifestyle choices, are

conventional medical treatments which not only ignore the cause of your illness, butadd more toxins to your body, in the form of pharmaceutical drugs.

 

The politics of toxic world 

Ample scientific evidence proves that we are being poisoned, slowly but surely, by all

these toxins permanently deposited in our bodies. Epidemic increase in the incidenceof degenerative diseases, for which our toxic exposures are among the main

causative factors, was "officially" ignored for a while, then partly acknowledged, buttreated mainly as a "drug deficiency".

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The danger of toxic substances in our air, food and water, was played down byassigning to them often convenient - to the industry and government - "safe limits".

That didn't make us safe. Not only that these "safe limits" are very loosely enforced.They are inherently arbitrary, which is why they keep shrinking as every next toxin

proves to be more, or much more damaging than what it was thought to be.

And no one ever bothered to access the

combined effect of hundreds of different chemical toxinspresent in our bodies. 

No wonder that the avalanche of degenerative diseases is not slowing down. Nowonder there is so many "clinically healthy" people suffering from serious,

sometimes debilitating symptoms. Or those others, who were "lucky" enough to geta disease label (diagnosis), but with the "cause unknown" tag attached. How do we

cure illnesses we don't know cause of? We don't...

While very few people doubt that we are exposed to many toxins, the majority is still

unwilling to accept that the effect can be so bad, as to cause widespread diseases.After all, there is the government, with institutions specifically monitoring healtheffects of chemicals in our air, water and food. Why would they allow such an

epidemic?

The answer is: (a) economic and political prosperity, and (b) the money power.Frankly, adequately protecting people's health would require production and

marketing constraints that would significantly slow down economic and politicalgrowth.

Evidently, governments have concluded long ago that strong economy and resultingpolitical power are

worth some sacrifice in the area of public health.

Financial power and political influence of large industrial conglomerates will makesure that this view doesn't change. But it got out of control: protecting "common"

interest is adversely affecting health of so many individuals, and to such a serious

extent, that it cannot be justified anymore. As more and more irrefutable evidence of poisoning surfaces, governments in developed countries - European more than the

U.S. - are getting involved.

However, it is occurring at such a large socioeconomic scale, that any significant

changes will require both enormous energy and years, if not decades of continuousefforts.

Taking care of yourself 

In the meantime, you need to be able to take care of your health, and health of 

those you care for the best you can. What the toxins piled up in your body do to yourhealth amounts to destruction: by interfering with vital body processes, they are

causing slow but steady degeneration, which ultimately manifests as a disease. They

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also rob your body of precious nutrients used up for detoxification, thus contribute tonutritional deficiencies, and to health problems resulting from them.

Significant reduction in toxic exposure, as well as in the level of toxins already

accumulated in your body, may require significant changes in your lifestyle. Brief body detox episodes should help a bit, but nothing can replace giving to the body

what it needs to detoxify, combined with minimizing your toxic exposure

daily. 

And that includes detoxifying: (1) your body, (2) your food, (4) your air and (5) your

water. Not to forget, you may need to detoxify your mind from toxic emotions. Yes,it is a handful but, just as with anything else, the more you invest, the greater

return. Obviously, for detoxification to be efficient you need to know

the toxins, where they come from,

and how to help your body get rid of them.

If you suffer from a disease, it is only more urgent. Freeing yourself from toxicplaque will give to your body a big boost in its fight against any developing, hidden

or full-blown illness.