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Published on: October 2, 2015
Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male rats
Yuuki Ohara1, Shan-Hwu Chew1, Takahiro Shibata1
1Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Abstract:
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 5 mg crocidolite i.p. to F1 hybrid rats between the Fischer-344 and Brown-Norway strains at the age of 6 weeks. We repeated weekly or biweekly phlebotomy of 6-8 mL/kg/time from 10 to 60 weeks of age. The animals were observed until 120 weeks. 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.
Insights
Phlebotomy, a method of iron removal, significantly reduced malignant mesothelioma (MM) development and improved survival in a rat model. This suggests phlebotomy could be a practical preventive strategy for asbestos-exposed individuals.
Area of Science:
- Oncology
- Toxicology
- Preventive Medicine
Background:
- Malignant mesothelioma (MM) is a rare cancer linked to asbestos exposure, with limited early diagnosis and treatment options.
- Asbestos exposure causes oxidative damage and MM through interactions with hemoglobin and histones.
- Previous studies showed iron chelators could prevent MM, but potential adverse effects necessitate alternative strategies.
Purpose of the Study:
- To investigate the efficacy of phlebotomy, a practical iron removal method, in preventing asbestos-induced malignant mesothelioma (MM).
- To evaluate phlebotomy's impact on MM development, progression, and survival in a rat model.
Main Methods:
- Rats were injected with crocidolite asbestos to induce MM.
- Phlebotomy (6-8 mL/kg) was performed weekly or biweekly from 10 to 60 weeks of age.
- Tumor characteristics, ascites, subtype, and survival were monitored until 120 weeks.
Main Results:
- Phlebotomy significantly reduced MM weight and nuclear grade in male rats.
- Phlebotomy modestly decreased ascites and the sarcomatoid subtype fraction.
- Weekly phlebotomy was associated with prolonged long-term survival.
Conclusions:
- Phlebotomy is a practical and potentially effective measure to mitigate asbestos-induced MM.
- Iron reduction through phlebotomy may attenuate the carcinogenic effects of asbestos.
- Phlebotomy shows promise as a preventive strategy for individuals with asbestos exposure.
