Benzene metabolites induce apoptosis in lymphocytes

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2006-08, Vol.58 (1), p.65-70
• Main Authors: Martínez-Velázquez, M., Maldonado, V., Ortega, A., Meléndez-Zajgla, J., Albores, A.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Benzene; Benzene - metabolism; Benzene - toxicity; Benzene Derivatives - toxicity; Biological and medical sciences; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - pathology; Cell Survival - drug effects; Culture Media, Conditioned - chemistry; Culture Media, Conditioned - metabolism; Culture Media, Conditioned - pharmacology; Detoxification; Environmental Pollutants - metabolism; Environmental Pollutants - toxicity; Gastroenterology. Liver. Pancreas. Abdomen; Hepatocyte; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; Hepatoma cell line; In vitro biotransformation; Investigative techniques, diagnostic techniques (general aspects); Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lymphocytes - drug effects; Lymphocytes - pathology; Male; Medical sciences; Muconic acid; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Rats; Rats, Wistar; Tumors
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2006.03.010

Benzene is an important environmental pollutant with important health implications. Exposure to this aromatic hydrocarbon is associated with hematotoxicity, and bone marrow carcinogenic effects. It has been shown that benzene induces oxidative stress, cell cycle alterations, and programmed cell death in cultured cells. Hepatic metabolism of benzene is thought to be a prerequisite for its bone marrow toxicity. Nevertheless, there are no reports on the cellular effects of reactive intermediates derived from hepatic metabolism of benzene. Thus, the goal of this project was to determine the cellular alterations of benzene metabolites produced by the cultured hepatic cell line HepG2. Supernatants collected from these cells were applied to a culture of freshly isolated lymphocytes. A higher decrease in cell viability was found in cells exposed to these supernatants than to unmetabolized benzene. This viability decrease was due to apoptosis, as determined by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) assay and internucleosomal fragmentation of DNA. When supernatants were analyzed by HPLC, we found that not all the hydrocarbon was biotransformed, since a 28 μM concentration (37%) remained. The only metabolite found in the culture medium was muconic acid. The present results show that muconic acid derived from benzene metabolism is able to cooperate with the pollutant for the induction of apoptosis in rat lymphocytes.