Larson David, Powers Amy, Ambrosi Jean-Paul, Tanji Mika, Napolitano Andrea, Flores Erin G, Baumann Francine, Pellegrini Laura, Jennings Cormac J, Buck Brenda J, McLaurin Brett T, Merkler Doug, Robinson Cleo, Morris Paul, Dogan Meral, Dogan A Umran, Pass Harvey I, Pastorino Sandra, Carbone Michele, Yang Haining
a University of Hawai'i Cancer Center , University of Hawai'i , Honolulu , Hawai'i , USA.
b CNRS, IRD, CEREGE UM34 , Aix-Marseille Université , Aix en Provence, France.
J Toxicol Environ Health B Crit Rev. 2016;19(5-6):213-230. doi: 10.1080/10937404.2016.1195321.
Similar to asbestos fibers, nonregulated mineral fibers can cause malignant mesothelioma (MM). Recently, increased proportions of women and young individuals with MM were identified in southern Nevada, suggesting that environmental exposure to carcinogenic fibers was causing the development of MM. Palygorskite, a fibrous silicate mineral with a history of possible carcinogenicity, is abundant in southern Nevada. In this study, our aim was to determine whether palygorskite was contributing to the development of MM in southern Nevada. While palygorskite, in vitro, displayed some cytotoxicity toward primary human mesothelial (HM) cells and reduced their viability, the effects were roughly half of those observed when using similar amounts of crocidolite asbestos. No Balb/c (0/19) or MexTAg (0/18) mice injected with palygorskite developed MM, while 3/16 Balb/c and 13/14 MexTAg mice injected with crocidolite did. Lack of MM development was associated with a decreased acute inflammatory response, as injection of palygorskite resulted in lower percentages of macrophages (p = .006) and neutrophils (p = .02) in the peritoneal cavity 3 d after exposure compared to injection of crocidolite. Additionally, compared to mice injected with crocidolite, palygorskite-injected mice had lower percentages of M2 (tumor-promoting) macrophages (p = .008) in their peritoneal cavities when exposed to fiber for several weeks. Our study indicates that palygorskite found in the environment in southern Nevada does not cause MM in mice, seemingly because palygorskite, in vivo, fails to elicit inflammation that is associated with MM development. Therefore, palygorskite is not a likely contributor to the MM cases observed in southern Nevada.
与石棉纤维类似，未经监管的矿物纤维可导致恶性间皮瘤（MM）。最近，在内华达州南部发现患有MM的女性和年轻人比例有所增加，这表明环境中致癌纤维的暴露导致了MM的发生。坡缕石是一种具有潜在致癌史的纤维状硅酸盐矿物，在内华达州南部储量丰富。在本研究中，我们的目的是确定坡缕石是否在内华达州南部MM的发生中起作用。虽然坡缕石在体外对原代人胸膜间皮（HM）细胞表现出一定的细胞毒性并降低了它们的活力，但其作用大约是使用等量青石棉时观察到的作用的一半。注射坡缕石的Balb/c小鼠（0/19）或MexTAg小鼠（0/18）均未发生MM，而注射青石棉的Balb/c小鼠中有3/16、MexTAg小鼠中有13/14发生了MM。缺乏MM的发生与急性炎症反应的降低有关，因为与注射青石棉相比，注射坡缕石后3天，腹腔中巨噬细胞（p = 0.006）和中性粒细胞（p = 0.02）的百分比更低。此外，与注射青石棉的小鼠相比，注射坡缕石的小鼠在接触纤维数周后，其腹腔中M2（促肿瘤）巨噬细胞的百分比更低（p = 0.008）。我们的研究表明，在内华达州南部环境中发现的坡缕石不会在小鼠中引起MM，这似乎是因为坡缕石在体内未能引发与MM发生相关的炎症。因此，坡缕石不太可能是在内华达州南部观察到的MM病例的致病因素。
