Cellular effects of asbestos and other fibers: correlations with in vivo induction of pleural sarcoma.

The phenomenon of fiber-induced cytotoxicity to P388D1 macrophagelike cells has been demonstrated to parallel (thus far without exception) the probability that the fiber will induce a pleural sarcoma (mesothelioma) in rats. This startling parallel in both cases seems to be essentially independent of the chemical nature of the fiber and correlates best with the presence of fibers greater than 8 micrometers in length and fibers with diameters in the range 0.5 to 1.0 micrometer (Stanton Hypothesis). In both systems evidence has been produced which cast strong doubts on any role played by absorbed (or adherent) impurities. The existence of multiple physical forms of the same chemical moiety (aluminum oxide, dihydroxy-sodium aluminum carbonate, borosilicate glass, etc.,) provides additional test material for the chemical independence corollary. The similar, cytotoxic or sarcomatogenous behavior of chemically different materials (e.g. amosite, chrysotile, aluminum oxide) exhibits the necessary converse argument. As long as the fiber size-shape dependency effect was limited to whole animal phenomena, such as tumor induction, one could make implicitly what were essentially statistical or probabilistic inferences involving transport and/or distribution of fibers to account for the physical effect. The demonstration of strict parallelism at the cellular level in vitro suggests the possibility that in the case of durable fiber toxicology we are dealing with a form of cell-solid interaction in which physical properties for which we have as yet no known receptors play a prominent role.