Epidemiological studies show that
benzene exposure is associated with an increased incidence of
leukemia and perhaps
lymphoma. Chromosomal rearrangements are common in these hematopoietic diseases. Translocation t(14;18), the long-arm deletion of chromosome 6 [del(6q)], and
trisomy 12 are frequently observed in
lymphoma patients. Rearrangements of the MLL gene located on chromosome 11q23, such as t(4;11) and t(6;11), are common in
therapy-related
leukemias resulting from treatment with
topoisomerase II inhibiting drugs. To examine numerical and structural changes in these chromosomes (2, 4, 6, 11, 12, 14, and 18), fluorescence in situ hybridization (FISH) was employed on metaphase spreads from workers exposed to
benzene (n = 43) and matched controls (n = 44) from Shanghai, China.
Aneuploidy (both
monosomy and
trisomy) of all seven chromosomes was increased by
benzene exposure.
Benzene also induced del(6q) in a dose-dependent manner (P(trend) = 0.0002). Interestingly, translocations between chromosomes 14 and 18, t(14;18), known to be associated with follicular
non-Hodgkin lymphoma, were increased in the highly exposed workers (P < 0.001). On the other hand, translocations between chromosome 11 and other partner chromosomes that are found in
therapy-induced
leukemias were not increased. These data add weight to the notion that
benzene can induce t(14;18) and del(6q) found in
lymphoma, but do not support the idea that
benzene induces t(4;11) or t(6;11). However, they do not rule out the possibility that other rearrangements of the MLL gene at chromosome 11q23 may be induced by
benzene.