This Article Full Text 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 Gowans, I. D. Articles by Wright, E. G. Search for Related Content PubMed PubMed Citation Articles by Gowans, I. D. Articles by Wright, E. G.

Genotype-Dependent Induction of Transmissible Chromosomal Instability by -Radiation and the Benzene Metabolite Hydroquinone

Division of Pathology and Neuroscience, University of Dundee Medical School, Dundee, United Kingdom

Requests for reprints: Eric G. Wright, Cancer Biology and Clinical Pathology Unit, Division of Pathology and Neurosciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, United Kingdom. Phone: 44-1382-632169; Fax: 44-1382-633952; E-mail: e.g.wright{at}dundee.ac.uk.

Although it is well established that ionizing radiation and benzene are epidemiologically linked to acute myeloid leukemia (AML), the underlying mechanisms are not understood. We have shown that -radiation can induce a persisting genomic instability in the clonal descendants of hemopoietic stem cells manifested as a high frequency of nonclonal chromosome and chromatid aberrations. A strikingly similar instability is shown after exposure to the benzene metabolite hydroquinone. The CBA/Ca but not the C57BL/6 genotype is susceptible to the induction of instability by both ionizing radiation and hydroquinone and exposure of CBA/Ca, but not C57BL/6, mice to either agent is known to be associated with the development of AML. The results are consistent with the proposal that chromosomal instability induced by either agent may contribute to AML development by increasing the number of genetic lesions in hemopoietic cells. Genotype-dependent chromosomal instability can be induced by hydroquinone doses that are not acutely stem cell toxic and this may have important implications for current assessment of safe levels of exposure to benzene as well as for mechanistic understanding of the hemotoxic and leukemogenic effects.

This article has been cited by other articles:

				M. S. Fox and S. Klawansky Interruption of cell transformation and cancer formation FASEB J, November 1, 2006; 20(13): 2209 - 2213. [Abstract] [Full Text] [PDF]

				M. Shen, Q. Lan, L. Zhang, S. Chanock, G. Li, R. Vermeulen, S. M. Rappaport, W. Guo, R. B. Hayes, M. Linet, et al. Polymorphisms in genes involved in DNA double-strand break repair pathway and susceptibility to benzene-induced hematotoxicity Carcinogenesis, October 1, 2006; 27(10): 2083 - 2089. [Abstract] [Full Text] [PDF]