Introduction
Mesothelioma is a cancer arising from the peritoneal and parietal pleural epithelium or subepithelium. Three main histological patterns are now recognized: epithelial, desmoplastic (a variant is sarcomatoid), and biphasic (mixed). Although there have been case reports with pathological descriptions consistent with the diagnosis since 1870, mesothelioma was not generally considered a distinct cancer entity until the 196Os (Jones, 2001 ). Special staining of tissue samples in use since 1985 has helped the clinical assessment of patients substantially by distinguishing most of the differential diagnoses of malignant mesothelioma, including "pseudomesothelioma" (Attanoos and Gibbs, 2003; Sporn and Roggli, 2004; Bueno et al., 2005). Mesotheliomas may develop spontaneously with no apparent link to any exposure-the same applies for most cancers, such as colon and breast malignancies (Doll and Peto, 1981; Spirtas et el., 1994; Meldrum, 1996; Hubbard, 1997; Roggli et al., 1997; Speizer, 2001; Roggli and Sharma, 2004; Patel et al., 2004; Price and Ware, 2004).
There are some known and suspected causes of mesothelioma (Peterson et al., 1984; Pelnar, 1988; Ilgren and Wagner, 1991; Hillerdal, 1999; Sato et al., 2000; Sporn and Roggli, 2004; Sterman, 2004; Lange, 2004). For example, epidemiological evidence indicates that some geologic minerals (e.g., the fibrous silicates erionite-zeolite) and other fibrous minerals such as "Libby amphibole" are associated with an elevated risk of mesothelioma. In the aftermath of the World Trade Center collapse on September 11, 2001, where widespread exposures to mainly chrysotile asbestos are reported, the long-running debate on the potency of chrysotile fibers of whatever physical dimensions to cause mesothelioma (and other health outcomes, which are beyond the scope of this review) hampers unambiguous risk communications (Landrigan et al., 2004; Lange, 2004; Greenberg, 2005; Nolan et al., 2005).
Asbestos is a commercial term used to describe minerals that share certain physical properties and is categorized into two families: serpentine (chrysotile) and amphiboles. Each asbestos type has a distinct chemical formula. Asbestos occurs both as asbestiform (fibrous) and nonasbestiform (massive) structures in nature, and each type retains its chemical composition in either form. Chrysotile is a sheet silicate that rolls into nano-sized tubular structures possessing a hollow core, whereas amphiboles are chain silicates.
Chrysotile is distinct not only in its chemistry, shape, and size distribution compared to the amphibole asbestos fibers, but also in its biopersistence in the lungs once inhaled. Based on multiple linear regression analyses of asbestos fiber content in human lung tissues, fibers (i.e., aspect ratio >3:1) of chrysotile longer than 10 µm have a half-life of 7.9 years, compared to 150.0 years for tremolite (Finkelstein and Dufresne, 1999); however, all fibers accumulate if lengths are over 18 µm in length for chronic exposures of workers (case et al., 2000). For fibers longer than 20 µm in animal studies, chrysotile asbestos from Calidria and Canadian mines cleared the lungs with a half-life of 7 hours and 11.5 days, respectively. By 2 days, all long Calidria fibers had dissolved/disintegrated into shorter pieces, and no long Canadian fibers were present after 1 year in the lung (Bernstein et al., 2005a, 2005b).
Of the multiple clearance mechanisms, an important factor for comparing biopersistence of fibers is dissolution rates. For in vitro studies under conditions analogous to biological systems, the measured dissolution rate for crocidolite is 40 times slower than for chrysotile. Dissolution of chrysotile fibers could be accelerated because chrysotile undergoes rapid, longitudinal splitting in the lung while amphiboles do not. Reportedly a chrysotile fiber with a diameter of 1 µm will dissolve in about 1 year, while a crocidolite fiber of the same diameter will take 60 years to dissolve. The distribution of the various asbestos fibers seen in lung tissue after a long period of time is the result of the dissolution and clearances of chrysotile asbestos fibers, compared to the amphiboles, and the amount and size distribution of the original aerosols such that the number of chrysotile fibers over 5 µm in length in the lung tends to be very small (Britton, 2002; Berman and Crump, 2003; Fattman et al., 2004; Bernstein et al., 2003,2005a). The final draft of the human risk assessment method for the U.S. Environmental Protection Agency (EPA), prepared by Berman and Crump and peer-reviewed by a panel of experts, assigns zero risk to fibers thinner than 0.4 µm and less than 10 µm in length for its optimized exposure index for mesothelioma (Berman and Crump, 2003, p. 7.49).
For purposes of research into its unique properties, the channels of chrysotile asbestos fibers have been filled under pressure by molten Hg, Sn, Bi, In, Pd, Se, and Te. These ultrathin, parallel filaments are similar to quantum wires in many ways and open the door to new microelectronic developments. Availability of synthetic chrysotile nanotubes with constant morphology and structure is crucial for nanotechnology because natural chrysotile has contamination with other minerals (Fe, Al, Ca, Ni, Mn, Na), contains different proportions of polytypes (ortho-para-clino-chTysotile), and is interspersed by its polymorphs lizardite and antigorite, whereas synthetic chrysotile does not possess these characteristics (Kumzerov et al., 2003; Falini, 2004). In view of these developments, elucidation of the true mesotheliogenic potency of natural chrysotile fibers absent of amphiboles has added importance in the rapidly emerging nanoparticle field in terms of occupational, consumer, environmental and medicinal exposures.