Asbestos: molecular action

Evidence for a Physical Process
Asbestos fibers alone do not induce oncogenic transformation at the concentrations examined. A higher number of sister chromatid exchanges were observed in cells treated with both asbestos and radiation compared to cells receiving radiation alone. The enhancement in radiation induced oncogenicity by asbestos fibers may be attributed to the mere physical presence of the fibers rather than any chemical contaminants the fibers may contain. Furthermore, the carcinogenicity of asbestos may be unrelated to genotoxicity.

[Hei TK et al; Br J Cancer 52 (4): 591-97 (1985)]**QC REVIEWED**

The physical presence of asbestos may cause asbestos-elicited macrophages to produce increased levels of superoxide and hydrogen peroxide. The supernatants from asbestos-elicited macrophages, which had been triggered in vitro, were capable of impairing the ability of alpha-1-protease inhibitor to inhibit elastase function. The catalase sensitivity of this effect showed it to be due to hydrogen peroxide.

[Weitzman SA, Weitberg AB; Biochem J 225 (1): 259-62 (1985)]**QC REVIEWED**

Evidence for a Chemical Process
An example of a direct chemical process that may cause tissue damage is the presence of trace metals (beryllium, cadmium, chromium, cobalt, copper, iron, manganese, nickel, or thallium) as natural impurities in asbestos or that may have been added inadvertently during milling and handling. The release of these contaminating metals in a biologically active form when the asbestos fibers are deposited in soft tissue may be involved in the cause of some asbestos-related diseases.

[Donaldson K et al; Inflammation 9 (2): 139-47 (1985)]**QC REVIEWED**

In this study, three different varieties of asbestos were found capable of catalyzing lipid peroxidation, a possible chemical mechanism for tissue injury. Pre-washing of the asbestos with the iron chelator desferroxamine inhibited this catalytic activity. Treatment with iron chelators might diminish the potential to produce this injury.

[Nat'l Research Council Canada; Effects of Asbestos in the Canadian Environ p.21 (1979) NRCC No. 16452]**QC REVIEWED**

Colon cancer in rats suggests that ingested asbestos is not inert in the colon. A chemical effect included in these results is the discovery that Cyclic-AMP levels in the colon were significantly lower in asbestos fed animals vs. controls.

A Combination of Physical and Chemical Factors Likely Lead to Tissue Damage and Disease

[Donham KJ et al; Cancer (March Suppl) 45: 1073-84 (1980) as cited in USEPA; Office of Drinking Water; Criteria Document (Draft): Asbestos p.VII-2 (1985)]**QC REVIEWED**