The Antioxidants Vitamins A and E and Selenium Do Not Reduce the Incidence of Asbestos-Induced Disease in a Mouse Model of Mesothelioma

Abstract

Epidemiological evidence indicates that supplementation with some dietary factors is associated with a lower incidence of cancer. An effective cancer prevention strategy for the millions of people worldwide who have been exposed to asbestos could have enormous benefit. We tested whether dietary supplementation of the antioxidants vitamin A, E, and selenium could alter the pattern of disease in the MexTAg transgenic mouse model, in which mice uniformly develop mesothelioma after asbestos exposure. We focused on antioxidants because one of the most widely accepted hypotheses for the mechanism by which asbestos fibers cause cancer proposes the involvement of reactive oxygen and nitrogen species. We compared the survival of MexTAg mice that had been inoculated with asbestos fed on diets supplemented with 250,000 IU/kg vitamin A (retinoic acid), or 1,000 mg/kg vitamin E (α-tocopherol acetate) or 3 mg/kg selenium, or both vitamin E and selenium concurrently and, additionally, diets deficient in each antioxidant. We found that neither the time to develop symptoms of disease nor overall survival times were altered by any of the diets. We conclude that the data do not support the notion that dietary antioxidants will moderate the rate of mesothelioma in asbestos-exposed populations.

Mouse Models of Mesothelioma: Strengths, Limitations and Clinical Translation

“…A successful prevention agent would be particularly useful for the millions of people worldwide who are living with a known asbestos exposure. Vitamins A, E, D and selenium and anti-inflammatory drugs were not found to have a benefit in the MexTAg model, despite a history of preventative activity and in vitro evidence for use against mesothelioma, findings that were confirmed for vitamin A and NSAIDs in a human cohort of asbestos-exposed workers from the Wittenoom crocidolite asbestos mines [70][71][72].…”

Serum Levels of Alpha-Tocopherol, Vitamin C, Beta-Carotene, and Retinol in Malignant Pleural Mesothelioma

“…But, low plasma levels of retinol associated with very modest increased risk of developing mesothelioma and lung cancer. However, a recent experimental study revealed that dietary supplementation with the antioxidant vitamins A and E, and selenium did not alter the rate of mesothelioma development and survival in transgenic mouse model (Robinson et al, 2012).…”

Selenium and exposure to fibrogenic mineral dust: A mini-review

“…In this line, previous studies have reported that very low levels of Se were a risk factor for the development of lung cancer, even if Se increases the risk of lung cancer mortality in people having high Se (Knekt et al, 1998;Fritz et al, 2011;El-Bayoumy, 2001;Suadicani et al, 2012). In vitro and animal studies have generated controversial data regarding the protective antioxidant effect of Se in fibrotic lung diseases (Robinson et al, 2012;Gabor et al, 1985;Janssen et al, 1990;Rose et al, 2014). Moreover, a great number of workers exposed to silica, asbestos, and coal dust are smokers (Wang and Christiani, 2000).…”

“…A study by Robinson et al failed to find a beneficial association between supplementing Se in the study outcome; they reported that Se supplementation to mice did not prolong survival after asbestos exposure or reduce the incidence of mesothelioma (Robinson et al, 2012), a lethal cancer due to asbestos exposure (Antman, 1993). However, various studies have demonstrated the increase of the Se-dependent enzyme glutathione peroxidase (hydrogen peroxide scavenging enzyme) or its mRNA upon silica or asbestos exposure as an adaptive response to the secretion of oxidants (Janssen et al, 1990(Janssen et al, , 1992.…”