Hematotoxicity, Leukemogenecity and Carcinogenecity of Chronic Exposure to Benzene

Autor: Muzaffer Aksoy
Rok vydání: 1991
Předmět:
Zdroj: Molecular Aspects of Monooxygenases and Bioactivation of Toxic Compounds ISBN: 9781468472868
DOI: 10.1007/978-1-4684-7284-4_24
Popis: As it is known benzene (C6H6) is the so called parent hydrocarbon of the aromatic group, the resonant cyclic compound consisting only of carbon and hydrogen. Benzene stems not only from industrial sources but it is present in natural products etc. On the other hand, incomplete combustion of all natural organic substances causes the formation of aromatic hydrocarbons. In this respect, tobacco smoke contains benzene in small amounts (1). Benzene is an excellent solvent for numerous solids. In addition, benzene is used in industry as a starting material in the production of numerous organic chemicals. Also, public exposure to benzene present in automobile gasoline ranging between 0.8 and 5 per cent has raised increased concern about this chemical agent as a significant environmental pollutant. Benzene is absorbed via the lungs and approximately 40 or 50 per cent of it is retained. Due to the high lipid solubility, benzene accumulates in fat and nervous system, and about 40-50 per cent of benzene with some carbon dioxide is excreted unchanged from the lungs. Furthermore, as Sherwood and Carter (2) showed that even after 24 hours a small percentage of benzene is exhaled unchanged. As it is known the major organ system implicated for benzene metabolism are the liver and the bone marrow. After inhalation, apart from insignificant traces of benzene in urine, most of the absorbed benzene remaining is ultimately metabolized into derivates which are more water soluble and thus more removable by the kidneys. The fact that the benzene metabolizing system is located in the cell microsomal fraction of the liver is demonstrated by differential centrifugation of the liver homogenate. The mixed function oxidases (mono-oxidases) in the endoplasmotic reticulum of the parenchym cells perform epoxidation of the nucleus to form arene oxides which decompose spontaneously to form phenol. Benzene oxide or epoxide, an unstable chemical which can attach to DNA or RNA giving cause to mutation. All these problems were discussed by Snyder (3) in the foregoing paper. Furthermore, recently Uyeki et al. (4) and later other investigators (5, 6) showed experimentally in mice that high doses of benzene such as 4680 or 4000 ppm cause rapid decrease of colony forming cells (CFC). These experiments (4, 5,6) and that of Post et al. (7) disclosed that benzene inhibits the self-renewal of pluropotent stem cells and that of the cells of microenvironment and by this phenomenon causes aplastic anemia. Furthermore, benzene is a suspected leukemogenic agent since the first description of a case of leukemia due to this chemical by Le Noire and Claude (8) in 1897. Recently Maltoni and Scarnato (9) showed in rats and mice that intake of high doses of benzene causes malignant tumours in several tissues. If an agent is toxic to the pluropotent stem cell or to microenvironment, it can cause an alteration in two important capabilities of the colony forming cells. These are: 1) Self renewal, and 2) Differentiation to produce a variety of lineage progenitor cells (10). In other words, the longterm maintenance of self-renewal and differentiation. Any block or disturbance in these capabilities will cause either aplastic anemia (a block in self-renewal) or leukemia (a block in differentiation).
Databáze: OpenAIRE