This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Erexson, G. L. Articles by Kligerman, A. D. Search for Related Content PubMed PubMed Citation Articles by Erexson, G. L. Articles by Kligerman, A. D.

Sister Chromatid Exchange Induction in Human Lymphocytes Exposed to Benzene and Its Metabolites in Vitro¹

Department of Genetic Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709

Previous in vivo studies have shown that low-dose benzene exposure (10 to 28 ppm for 4 to 6 h) in mice can induce sister chromatid exchange (SCE) in peripheral blood B-lymphocytes and bone marrow as well as micronuclei in bone marrow polychromatic erythrocytes. Because benzene is metabolized to a variety of intermediate compounds and two of these, catechol and hydroquinone, have been reported to be potent SCE-inducers, it is possible that other known and proposed metabolites could have chromosome-damaging effects in lymphocytes. Induced SCE frequencies, mitotic indices, and cell cycle kinetics were quantitated in human peripheral blood T-lymphocytes exposed to benzene, phenol, catechol, 1,2,4-benzenetriol, hydroquinone, 1,4-benzoquinone, or trans,trans-muconic acid. Three proposed metabolites of phenol, 4,4'-biphenol, 4,4'-diphenoquinone, and 2,2'-biphenol, which can be generated by a phenolhorseradish peroxidase-hydrogen peroxide system were also examined. Benzene, phenol, catechol, 1,2,4-benzenetriol, hydroquinone, and 1,4-benzoquinone induced significant concentration-related increases in the SCE frequency, decreases in mitotic indices, and inhibition of cell cycle kinetics. Based on the slope of the linear regression curves for SCE induction, the relative potencies were as follows: catechol > 1,4-benzoquinone > hydroquinone > 1,2,4-benzenetriol > phenol > benzene. On an induced SCE per µM basis, catechol was approximately 221 times more active than benzene at the highest concentrations studied. trans,trans-Muconic acid had no significant effect on the cytogenetic parameters analyzed. 2,2'-Biphenol induced a significant increase in SCE only at the highest concentration analyzed, and 4,4'-biphenol caused a significant increase in SCE frequency that was not clearly concentration related. However, both 2,2'- and 4,4'-biphenol caused significant cell cycle delay and mitotic inhibition. 4,4'-Diphenoquinone caused only a significant decrease in mitotic activity. These data indicate that in addition to phenol, di- and trihydroxybenzene metabolites play important roles in SCE induction. Furthermore, the results suggest either that benzene alone can induce SCE or, a more likely possibility, that mononuclear leucocytes have a limited capability to activate benzene.

¹ This research was funded by the Chemical Industry Institute of Toxicology, a privately funded institute.

² Present address: Environmental Health Research and Testing, Inc., P. O. Box 12199, Research Triangle Park, NC 27709. To whom requests for reprints should be addressed.

³ Present address: Environmental Health Research and Testing, Inc., P. O. Box 12199, Research Triangle Park, NC 27709.

Received 1/21/85. Revised 3/11/85. Accepted 3/12/85.

This article has been cited by other articles:

				H. Ahmad Khan Short Review: Benzene's toxicity: a consolidated short review of human and animal studies Human and Experimental Toxicology, September 1, 2007; 26(9): 677 - 685. [Abstract] [PDF]

				P. J. Spencer, B. B. Gollapudi, and J. M. Waechter Jr Induction of Micronuclei by Phenol in the Mouse Bone Marrow: I. Association with Chemically Induced Hypothermia Toxicol. Sci., May 1, 2007; 97(1): 120 - 127. [Abstract] [Full Text] [PDF]

				M. T. Smith, L. Zhang, M. Jeng, Y. Wang, W. Guo, P. Duramad, A. E. Hubbard, G. Hofstadler, and N. T. Holland Hydroquinone, a benzene metabolite, increases the level of aneusomy of chromosomes 7 and 8 in human CD34-positive blood progenitor cells Carcinogenesis, August 1, 2000; 21(8): 1485 - 1490. [Abstract] [Full Text] [PDF]