| Summary: | BACKGROUND: Benzene is a widely used solvent and is used in the production of many chemicals and gasoline. Benzene is known to cause cancer in laboratory animals and leukemia in humans. We tested benzene in a genetically modified mouse strain that lacks two tumor suppressor genes as part of a study to determine if this mouse model could detect cancer-causing chemicals more rapidly than the standard 2-year rodent bioassay. METHODS: We exposed groups of male or female haploinsufficient p16Ink4a/p19Arf mice by depositing solutions of benzene in corn oil directly into the animals' stomachs through a tube five times per week for 27 weeks. The daily doses were 25, 50, 100, or 200 milligrams of benzene per kilogram of body weight; other animals receiving only corn oil served as the control groups. Tissues from 22 organs were examined for every animal. RESULTS: Exposure to benzene caused malignant lymphomas in male haploinsufficient p16Ink4a/p19Arf mice receiving the greatest dose of benzene. Other effects seen in male mice included bone marrow atrophy, hematopoietic cell proliferation in the spleen, and atrophy of the thymus and lymph nodes. No increased incidences of cancer were seen in female haploinsufficient p16Ink4a/p19Arf mice, though atrophy of the mesenteric lymph nodes was observed. CONCLUSIONS: We conclude that benzene caused malignant lymphoma in male haploinsufficient p16Ink4a/p19Arf mice but not in females
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