Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene

Abstract

Benzene is used as a general purpose solvent. Benzene metabolism starts from phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by benzene still remains a toxicologic problem. Tumor related genes and immune responsive genes have been studied in patients suffering from benzene exposure. However, gene expression profiles and pathways related to its hepatotoxicity are not known. This study reports the results obtained in the liver of BALB/C mice (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji., Japan). Histopathological observations were made to support gene expression data. c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After six days of benzene exposure, twenty five genes were down regulated whereas nineteen genes were up-regulated. These gene expression changes were found to be related to pathways of biotransformation, detoxification, apoptosis, oxidative stress and cell cycle. It has been shown for the first time that genes corresponding to circadian rhythms are affected by benzene. Results suggest that gene expression profile might serve as potential biomarkers of hepatotoxicity during benzene exposure.

Melatonin Improves Liver Function in Benzene-Treated Rats

“…Our gene expression study (29) also confirmed that downregulation of CYP2610 and CYP4A10 genes after benzene treatment accounts for biochemical and histopathological changes in BALB/c mice. We also observed that circadian rhythm affects benzeneinduced lipid peroxidation (30).…”

Environmental risk factors of systemic sclerosis

“…Other experimental models have shown that exposure to trichloroethylene led to (1) protein modifications [55][56][57][58][59]; (2) synthesis of higher levels of IL-17 and IL-21 by splenocytes in trichloroethylene-treated mice [60]; (3) production of reactive oxygen species and increased nitric oxide by nitric oxide synthase in cultured human epidermal keratinocytes [61]; (4) Th1 T cell activation in MRL+/+ mice [62]; (5) inhibition of cellular apoptosis of naïve CD4+ and CD8+ T cells in MRL+/+ mice [63]; and (6) DNA hypermethylation on rat cardiac myoblasts [64]. Furthermore, other experimental studies have shown that exposure to benzene resulted in (1) decreased T cell population in wild/captive American kestrel birds [65]; (2) reduced number of CD4+/CD8+ T cells and B cells in exposed workers [66]; (3) increased reactive oxygen species and induction of DNA fragmentation in pump workers [67]; and (4) changes in gene transcription involved in apoptosis, oxidative stress, cellular cycle, and cytokine production in benzene-treated mice [68].…”

Melatonin Inhibits Benzene-Induced Lipid Peroxidation in Rat Liver

“…In contrast, other reports indicate benefi cial effects of melatonin on arsenic-induced oxidative stress in the liver and kidney of Wistar rats (18). It was shown recently that expression of genes responsible for oxidative stress and detoxifi cation enzymes is altered by benzene in mice (40). Genes corresponding to the circadian rhythm were also affected by benzene (40).…”

“…It was shown recently that expression of genes responsible for oxidative stress and detoxifi cation enzymes is altered by benzene in mice (40). Genes corresponding to the circadian rhythm were also affected by benzene (40). Several reports have confi rmed that antioxidative effects of melatonin are caused by at least two different mechanisms, which might, however, be interdependent (41).…”