Journal
CANCER SCIENCE
Volume 109, Issue 2, Pages 330-339Publisher
WILEY
DOI: 10.1111/cas.13460
Keywords
asbestos; malignant mesothelioma; oxidative stress; phlebotomy; prevention
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Funding
- Japan Society for the Promotion of Science [JP17H04064, JP221S0001-04, JP24108008]
- Private University Research Branding Project
- Takeda Science Foundation Fellowship
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Malignant mesothelioma (MM) is a rare but socially important neoplasm due to its association with asbestos exposure. Malignant mesothelioma is difficult to diagnose at an early stage, yet there are no particularly effective treatments available at the advanced stage, thus necessitating efficient strategies to prevent MM in individuals already exposed to asbestos. We previously showed that persistent oxidative damage caused by foreign body reaction and affinity of asbestos both to hemoglobin and histones is one of the major pathogeneses. Accordingly, as an effective strategy to prevent asbestos-induced MM, we undertook the use of an iron chelator, deferasirox, which decreased the epithelial-mesenchymal transition in a crocidolite-induced rat MM model. However, this agent may show adverse effects. Here, we studied the effects of iron removal by phlebotomy as a realistic measure on the same rat model. We injected a total of 5mg crocidolite i.p. to F1 hybrid rats between the Fischer-344 and Brown-Norway strains at the age of 6weeks. We repeated weekly or biweekly phlebotomy of 6-8mL/kg/time from 10 to 60weeks of age. The animals were observed until 120weeks. In male rats, phlebotomy significantly decreased the weight and nuclear grade of MM, and modestly reduced the associated ascites and the fraction of more malignant sarcomatoid subtype. Weekly phlebotomy prolonged long-term survival. Our results indicate that appropriate phlebotomy may be a practical preventive measure to attenuate the initiation and promotion capacity of asbestos towards MM by reducing iron in individuals exposed to asbestos.
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