Benzene

I. Medical history: How is it used in medicine and what disease it is used against.

Benzene is a common air pollutant and also is a very stable compound. Benzene, in its original form is known to produce neurotropic symptoms as well as hematological abnormalities and malignancies. It is also a known carcinogen. Benzene, at high temperatures, pressures and catalysts, reacts with other compounds give a variety of substances that has medicinal value. Some of these compounds are discussed below.

1. p amino benzene sulphonamide (sulfanilamide), found in prontosil, an azo dye, is an active therapeutic agent. This drug was greatly effective and specific against various bacterial diseases. The prontosil dye is also used against hemolytic streptococcal infection among humans. Sulfanilamide is effective against beta hemolytic streptococci, meningococci, gonococci, C1 Welchii and several other types of bacteria. The drug has a greater activity in vivo which suggest that the humoral and cellular defense mechanism of the organism contribute to its efficacy. It is extremely effective against virulent bacteria. The use of this drug has markedly reduced the mortality of pneumonia. Infections of meningococci meningitis, gonorrhea, urinary tracts infection and other common and serious infections are effectively and promptly cured. Due to the limited effect on certain organisms like pnemococci, there was a subsequent quest for substituted sulfanilamides. They are as follows:
   1. Sulfapyridine (2 sulfanilyl amino pyridine): It is used in the therapy of pneumococcal infections.
   2. Sulfathiazole: Also used in pneumococcal infections and also acts successfully against staphylococci.
   3. Sulfadiazine: Similar in action to sulfathiazole.
2. Benzodiazepines, a compound where a benzene ring is fused to a seven sided diazepine ring and also have a second benzene ring, also is used in medicines. These drugs are used in generalized anxiety disorders, panic disorders and social phobia. These are also used for insomnia. This drug has a high effect in the treatment of bipolar I disorder and for agitation in many disorders including schizophrenia. It is also a valuable medicine in the treatment of anti psychotic induced akathesia, a type of restlessness. Some benzodiazipines have an anti depressant effect. Drugs in this class are also used as a pre treatment of epilepsy and muscle spasms. They are also used as a pre treatment for some quasi surgical procedures and to help patients withdraw from cross tolerant substances such as alcohol and barbituarates.
3. Aspirin: It is also known as acetyl salicylic acid. It is used as an analgesic to relieve minor aches and pains and as an anti pyretic to reduce fever. It is also used as an anti inflammatory medication. This is given in low doses to prevent heart attacks and used as a remedial measure to developing blood clots.

II. Toxicity: What makes it toxic?

Benzene being a common air pollutant is capable of producing neurotoxic symptoms as well as hematologic abnormalities and malignancies. It is also a known carcinogen. Studies have shown that exposure to benzene can be the cause of a variety of blood and bone marrow disorders, including leucopenia, anemia, myelodysplastic syndrome, acute aplastic anemia, acute leukemia and acute lymphocytic leukemia.
Benzene reactivity results from its intermediate reactive metabolites. Some of these are phenol, hydroquinone, catechol and transmuconic acid. These actually initiate the toxic effect on an organ. Benzene is initially oxidized to benzene oxide by hepatic CYP2E1 in the liver. Benzene oxides form phenol spontaneously conjugates with glutathione to form less toxic or non toxic derivative via glutathione S transferases. Phenol is catalyzed by CYP2E1 to potentially toxic di or tri hydroxybenzenes such as hydroquinone, catechol and 1,2,4, benzene triol. The di or trihydroxy metabolites are further oxidized in the bone marrow by myeloperoxidase to benzoquinone, a potent hematotoxic and genetic agent. Its effect in bone marrow may be enacted through multiple pathways, including growth factor regulation, DNA damage repair, cell cycle regulation and apoptosis. Hence it induces not only hemopoietic cellular damage but also the dysfunction of bone marrow stromal cells.
Bone marrow tissue is one of the major target organ of benzene and an active hemopoietic system in which various genes that maintain cellular environmental homeostasis are organized their network interactions as well as protect cells from endogenous and exogenous hematotoxic effects such as benzene induced effects. The dysregulation of such a multidimensional counterbalance induced by the genetic and epigenetic effect of benzene may result in the altered expression of a member of the gene thereby inducing hematotoxicity and leukemogenicity.
Benzene is a well known clastogen that requires metabolic activities to be mutagenic. The genotoxic metabolites are also thought to play an important role in benzene mylotoxicity and leukemogenesis. The quinine metabolites of benzene can break chromosomes by inducing reactive oxygen species but may also act as euploidogens causing microtubule disruption.
The strong and repeated genetic and epigenetic effects of a benzene on leukemia cell possibly cause the dysfunction of the p53 gene thus resulting in fatal malfunctions. Exposure duration and dose are also important factors in determining benzene induced hematotoxicity and leukemogenecity. This may be related to the dynamic responses of hemopoietic micro environmental conditions against the adverse effects of benzene and the limited capacity of enzymes for benzene metabolism.

III. Diseases and harmful things that happen after inhaling it: What it does to the human body.

The hematotoxic and leukemogenic properties of benzene make it dangerous to human body. Major release of benzene arise from the use of crude oil, gasoline and chemical industry emissions. Benzene is highly volatile. The prevalent form of exposure to benzene is by inhalation, ingestion of food and water, and by direct contact, mainly with products containing benzene such as gasoline. Benzene and its metabolites seem to be genotoxic to humans, causing primarily chromosomal aberrations. Chronic exposure to benzene has been associated with leukemia and other cancers. It also results in malignant lymphoma and neoplastic diseases of the blood. Its toxic effect on the blood and bone marrow include leucopenia, pancytopenia and aplasic anemia and is also an established cause of human leukemia.
The strong and repeated genetic and epigenetic effects of benzene on leukemia cells possibly cause the dysfunction of the p 53 gene, and may induce fatal problems such as those of cell cycle disorder, apoptosis and DNA repair system, finally resulting in hemopoietic malignancies. Benzene metabolizes into reactive metabolites like phenol, hydroquinone etc. by hepatic enzymes, and these subsequently undergo secondary activation by myeloperoxidase present in the bone marrow tissue. This results in the production of genotoxic hemopoietic cellular damage but also the dysfunction of the bone marrow stromal cells. Exposure duration and dose are also important factors in determining benzene induced hemotoxicity and leukemogenicity. These are also related to the limited capacity of enzyme for benzene metabolism and also to the dynamic responses of hemopoietic micro environmental conditions.
Bone marrow tissue is one of the major targets of benzene and also is an active hemopoietic system in which various counter balanced genes are organized through their network interactions that maintain cellular environmental homeostasis and also protect cells form endogenous and exogenous hemetotoxic effect such as those by benzene. The genetic and epigenetic effects of benzene possibly causes the dysregulation of such a multidimensional counterbalance that may result in the altered expression of a number of genes associated with the benzene induced hematotoxicity and leukemogenecity.
In liver, benzene is oxidized to benzene oxide by hepatic CYP2E1. This benzene oxide forms phenol spontaneously or conjugates with glutathione S Transferases. Phenol is then catalyzed by CYP2E1 to potentially toxic di or trihydroxy benzenes such as hydroquinone, catechol and 1,2,4, benzene triol. The di or trihydroxy metabolites are further oxidized in the bone marrow by myeloperoxidase to benzoquinones, a potent hematotoxic and genetic agent.