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Increased Translocations and Aneusomy in Chromosomes 8 and 21 Among Workers Exposed to Benzene¹

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California 94720-7360 [M. T. S., L. Z., Y. W., J. W., N. T-H., P. K.]; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892 [R. B. H., M. D., N. R.]; and Institute of Occupational Medicine, Chinese Academy of Preventive Medicine, Beijing 100050, China [G. L., L. X., S. Y.]

Chromosome aberrations in peripheral blood lymphocytes have been used for many years to monitor human populations exposed to potential carcinogens. Recent reports have confirmed the validity of this approach by demonstrating that elevated levels of chromosome aberrations in lymphocytes are associated with subsequent increased cancer risk, especially for increased mortality from hematological malignancies including acute myeloid leukemia (AML). We postulated that this approach could be improved in two ways: (a) by detecting oncogenic disease-specific aberrations; and (b) by using chromosome painting so that many more metaphases could be analyzed. Numerical and structural aberrations in chromosomes 8 and 21 are commonly observed in AML. In the present study, we painted chromosomes 8 and 21 in lymphocyte metaphases from 43 healthy workers exposed to benzene, an established cause of AML, and from 44 matched controls. To examine dose-response relationships the workers were divided into two groups at the median exposure level, a lower-exposed group ( 31 ppm; n = 21), and a higher-exposed group (>31 ppm; n = 22). Benzene exposure was associated with significant increases in hyperdiploidy of chromosomes 8 (1.2, 1.5, and 2.4 per 100 metaphases; P < 0.0001) and 21 (0.9, 1.1, and 1.9 per 100 metaphases; P < 0.0001). Translocations between chromosomes 8 and 21 were increased up to 15-fold in highly exposed workers (0.01, 0.04, and 0.16 per 100 metaphases; P < 0.0001). In one highly exposed individual, these translocations were reciprocal and were detectable by reverse transcriptase-PCR. These data indicate a potential role for t(8;21) in benzene-induced leukemogenesis and are consistent with the hypothesis that detection of specific chromosome aberrations may be a powerful approach to identify populations at increased risk of leukemia.

¹ Supported by funds from the National Cancer Institute; National Institute of Environmental Health Sciences Grants RO1 ES06721, P42 ES04705, and P30 ES01896; and a grant from the California Environmental Protection Agency (to M. T. S.). J. W. was supported by a Howard Hughes Predoctoral Fellowship.

² To whom requests for reprints should be addressed, at Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720-7360.

Received 11/14/97. Accepted 3/17/98.

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