Cytotoxicity and DNA Strand Breaks Induced by Benzene and its Metabolites in Chinese Hamster Ovary Cells

Abstract

The cytotoxicity of benzene (BZ) and its major metabolites phenol (PHE), hydroquinone (HQ), catechol (CAT), 1,4-benzoquinone (BQ), 1,2,4-benzenetriol (BT), trans,trans-muconic acid (ttMA) and S-phenylmercapturic acid (S-PMA) was assessed by exposing Chinese Hamster Ovary (CHO) cells to these compounds. Benzene was the least toxic (LD50 = 20 mM), while BQ showed the highest potency (LD50 = 10 μM), followed by HQ (LD50 = 40 μM). It was found that the trend of cytotoxicity was: BQ > HQ >> CAT > ttMA > BT > S-PMA >> PHE > BZ. 1,4-Benzoquinone and HQ also demonstrated considerable ability to induce DNA strand breaks in CHO cells, which was assayed using the fluorimetric analysis of DNA unwinding. The other metabolites were unable to cause DNA strand breaks. When HQ was administered in combination with other metabolites, no synergism was observed in the induction of DNA strand breaks. From these results, it can be seen that BQ and HQ are the most bioreactive species among the benzene metabolites when tested on CHO cells. Differences between the results obtained in our study and other studies were discussed.