Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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Type: other: The benzene metabolite, hydroquinone, selectively
induces 5q31– and –7 in human CD34+CD19– bone marrow cells.
Remark: OBJECTIVE: Chronic exposure to high concentrations of
benzene is associated with an increased incidence of
myelodysplastic syndrome and acute myelogenous leukemia.
Acute myelogenous leukemia developing in patients treated
with alkylating agents for other cancers or occupationally
exposed to benzene exhibit a pattern of cytogenetic
aberrations predominantly involving loss of all or part of
chromosomes 5 and/or 7. In contrast, trisomy 8 is observed
equally in both de novo and secondary acute myelogenous
leukemia. Studies using peripheral lymphocytes or
lymphoblastoid cell lines have observed dose–dependent loss
of chromosomes 5, 7, and 8 following treatment with the
benzene metabolite, hydroquinone. The purpose of this study
was to determine the dose response and specificity of
hydroquinone–induced aberrations on chromosomes 5, 7, and 8
using human CD34+CD19 bone marrow cells. MATERIALS AND
METHODS: Fluorescence in situ hybridization analysis was
performed on CD34+CD19– bone marrow cells using the
locus–specific probes, 5q31, 5p15.2, and centromeric probes
specific for human chromosomes 7 and 8 following
hydroquinone exposure. RESULTS: Hydroquinone exposure
results in –7, selective deletion of 5q31 but not chromosome
5 and no loss or gain of chromosome 8 in human CD34+CD19–
cells. CONCLUSION: CD34+ bone marrow cells are more
susceptible and show a different pattern of cytogenetic
aberrations as a result of hydroquinone exposure compared to
lymphocytes. CD34+ bone marrow cells exhibit unique
susceptibility to the development of specific chromosome
aberrations that have been identified as the earliest
structural changes occurring in the development of secondary
myelodysplastic syndrome and acute myelogenous leukemia.
Source: EXXON Biomedical Sciences East Millstone, NJ
Reliability: (1) valid without restriction
24–JUL–2000 (1089)
Type: other: Genetic effects of petroleum fuels: II. Analysis of
chromosome loss and hyperploidy in peripheral lymphocytes of
gasoline station attendants.
Remark: Molecular cytogenetic methods were applied to investigate
the effect of the occupational exposure to low
concentrations of benzene and petroleum fuels on genomic
stability. Twelve male gasoline station attendants (average
benzene exposure of 0.32 mg/m3 as 8h TWA) and 12 age– and
smoking–matched unexposed controls were selected for the
study. The incidence of hyperploidy and polyploidy in
peripheral lymphocytes was evaluated through in situ
hybridization of interphase cells, harvested 24 hr after
stimulation, with centromeric probes of chromosomes 7, 11,
18, and X. For half of the subjects, metaphases harvested 24
hr later were analyzed. The incidence of chromosome loss in
vitro was determined in cytokinesis–blocked cells, harvested
at 66 hr, through the hybridization of micronuclei with a
Appendix D: Benzene SIDS Dossier
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