• heterozygotes show a significantly higher incidence and accelerated onset of asbestos-induced malignant mesothelioma (MM), with abdominal swelling noted as early as 20 wks after the first asbestos injection versus 27 wks in wild-type controls
• ultimately, 90% of asbestos-exposed heterozygotes showed abdominal distention, with ~60% of these containing ascites; almost all showed liver anomalies, pancreatic fibrosis, intestinal adhesions, and thickenings of the peritoneum, mesentery, and diaphragm
• heterozygotes exhibited a median survival of 43 wks after initial asbestos exposure versus 55 wks in wild-type controls; 73% of deaths occurred due to peritoneal MM, relative to only 32% in wild-type controls
• although all asbestos-exposed heterozygotes died from MM and other asbestos-related disease by 57 wks, 20% of wild-type controls remained alive and asymptomatic at this time
• in heterozygotes, asbestos-induced MMs were significantly larger and more aggressive than those in wild-type controls, often invading the pancreas, liver, and/or intestinal smooth muscle; occasional metastasis to the lungs was observed
• Ki-67 staining revealed a higher proliferative index in heterozygous MMs relative to wild-type MMs
• in culture, MM cells derived from asbestos-exposed heterozygotes showed loss of expression of the wild-type Bap1 allele, consistent with loss of heterozygosity
• no spontaneous mesotheliomas were detected in untreated heterozygotes up to 87 wks of age
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